Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro

Detalhes bibliográficos
Autor(a) principal: BORGES, Guilherme Henrique
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/781
Resumo: O carcinoma epidermoide oral é uma neoplasia epitelial responsável pela maioria das lesões malignas que acometem a região de cabeça e pescoço. O e o Y-27632 são inibidores das ROCKs, que são efetoras das GTPases Rho, e estão associadas à patogênese e progressão de tumores humanos. Este estudo visou avaliar o papel funcional das ROCKs na regulação da proliferação de células SCC-4 de carcinoma epidermoide oral in vitro. Foram quantificadas as células SCC-4 de carcinoma epidermoide oral controle e tratadas com HA-1077 (25, 50 e 100 μM) por 6 e 24 horas; e HA-1077 (25, 50 e 100 μM), HA-1077 50 µM e/ou Y-27632 30 µM por 6 horas, em ensaios de incorporação de BrdU e imunoexpressão de KI-67. Foi considerado significante p<0,05. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM) que incorporaram BrdU foi significativamente menor que o de células controle em 6 horas [F(3,11) = 107,461, p<0,0001] e 24 horas [F(3,11) = 167,433, p<0,0001], de modo dose dependente. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM), HA- 1077 50 µM e/ou Y-27632, por 6 horas, que incorporaram BrdU [F(5,17) = 443,818, p<0,0001], e o número que imunoexpressaram KI-67, também, foi significativamente menor [F(5,17) = 192,595, p<0,0001], que o de células controle. Os resultados obtidos sugerem que as proteínas ROCKs desempenham um papel funcional importante na regulação da proliferação celular em carcinoma epidermoide oral, uma vez que o HA-1077 e/ou o Y- 27632, inibidores de ROCKs, têm um efeito inibitório sobre a proliferação de células SCC-4.
id UFTM_951f3a43d50cc8ac83233c2783a97726
oai_identifier_str oai:bdtd.uftm.edu.br:tede/781
network_acronym_str UFTM
network_name_str Biblioteca Digital de Teses e Dissertações da UFTM
repository_id_str
spelling Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitroCarcinoma de epidermoide oral.HA-1077.Proliferação celular.ROCKs.Y-27632.Oral squamous cell carcinoma.HA-1077.Cell proliferation.ROCKs.Y-27632.MorfologiaCitologia e Biologia CelularO carcinoma epidermoide oral é uma neoplasia epitelial responsável pela maioria das lesões malignas que acometem a região de cabeça e pescoço. O e o Y-27632 são inibidores das ROCKs, que são efetoras das GTPases Rho, e estão associadas à patogênese e progressão de tumores humanos. Este estudo visou avaliar o papel funcional das ROCKs na regulação da proliferação de células SCC-4 de carcinoma epidermoide oral in vitro. Foram quantificadas as células SCC-4 de carcinoma epidermoide oral controle e tratadas com HA-1077 (25, 50 e 100 μM) por 6 e 24 horas; e HA-1077 (25, 50 e 100 μM), HA-1077 50 µM e/ou Y-27632 30 µM por 6 horas, em ensaios de incorporação de BrdU e imunoexpressão de KI-67. Foi considerado significante p<0,05. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM) que incorporaram BrdU foi significativamente menor que o de células controle em 6 horas [F(3,11) = 107,461, p<0,0001] e 24 horas [F(3,11) = 167,433, p<0,0001], de modo dose dependente. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM), HA- 1077 50 µM e/ou Y-27632, por 6 horas, que incorporaram BrdU [F(5,17) = 443,818, p<0,0001], e o número que imunoexpressaram KI-67, também, foi significativamente menor [F(5,17) = 192,595, p<0,0001], que o de células controle. Os resultados obtidos sugerem que as proteínas ROCKs desempenham um papel funcional importante na regulação da proliferação celular em carcinoma epidermoide oral, uma vez que o HA-1077 e/ou o Y- 27632, inibidores de ROCKs, têm um efeito inibitório sobre a proliferação de células SCC-4.The oral carcinoma cell squamous (OSCC) is epithelial cancer responsible for the majority of malignant lesions affecting the head and neck region. The HA-1077 and the Y-27632 are inhibitors of the ROCKs which are effector of Rho GTPases, and are associated with pathogenesis and progression of human tumors. This study aimed to evaluate the functional role of the ROCKs in the regulation of cellular proliferation of SCC-4 cell line from OSCC. Control cells and cells treated with HA-1077 (25, 50 and 100 μM) were quantified for 6 and 24 hours; and HA-1077 (25, 50 and 100 μM), HA-1077 50 µM and/or Y-27632 30 µM for 6 hours, in BrdU assays and immunoexpression of KI-67 assays. Was considered significant p<0.05. The number of SCC-4 cells treated with HA-1077 (25, 50 and 100 μM) that incorporated BrdU was significantly lower than control cells in 6 hours [F (3.11) = 107.461, p<0.0001] and 24 hours [F (3.11) = 167.433, p<0.0001], therefore dose dependent. The number of proliferative SCC-4 cells treated with HA-1077 (25, 50 and 100 μM), HA-1077 50 µM and/or Y-27632, for 6 hours, in BrdU assay [F (5.17) = 443.818, p<0.0001], and in imunoexpressaram KI-67 assay, also, was significantly less [F (5.17) = 192.595, p<0.0001], than control cells. The results obtained suggest that the ROCKs play an important functional role in the regulation of cellular proliferation in OSCC, since both HA-1077 and/or the Y- 27632, inhibitors of ROCKs, have an inhibitory effect on proliferation of SCC-4 cells.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de Minas GeraisUniversidade Federal do Triângulo MineiroUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeCREMA, Virgínia Oliveira66127211620http://lattes.cnpq.br/2599388555203811BORGES, Guilherme Henrique2019-07-22T14:25:45Z2017-11-22info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfBORGES, Guilherme Henrique. Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro. 2017. 74f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2017.http://bdtd.uftm.edu.br/handle/tede/781porABE, H. et al. The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer, v. 14, p. 412, 2014. ISSN 1471-2407. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24908363 >. ADNANE, J. et al. Suppression of rho B expression in invasive carcinoma from head and neck cancer patients. Clin Cancer Res, v. 8, n. 7, p. 2225-32, Jul 2002. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12114424 >. ALBERTS, B. E. A. Molecular Biology of The Cell 5a. 2008. 1268. AMANO, M.; NAKAYAMA, M.; KAIBUCHI, K. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken), v. 67, n. 9, p. 545-54, Sep 2010. ISSN 1949-3592. Disponível em: <http://www.ncbi.nlm.nih.gov/pubmed/20803696 >. AMANO, M. et al. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase. PLoS One, v. 5, n. 1, p. e8704, Jan 2010. ISSN 1932- 6203. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20090853 >. ASANO, T. et al. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther, v. 241, n. 3, p. 1033-40, Jun 1987. ISSN 0022-3565. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/3598899 >. BAGAN, J. V.; SCULLY, C. Recent advances in Oral Oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral Oncol, v. 44, n. 2, p. 103-8, Feb 2008. ISSN 1368-8375. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/18252251 >. ______. Recent advances in Oral Oncology 2008; squamous cell carcinoma aetiopathogenesis and experimental studies. Oral Oncol, v. 45, n. 7, p. e45-8, Jul 2009. ISSN 1879-0593. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19196543 >. BARNES, L.; EVERSON, J. W.; REICHART, P. World health organization classification of tumours pathology and genetics of head and neck tumours. 2005. BIRO, M.; MUNOZ, M. A.; WENINGER, W. Targeting Rho-GTPases in immune cell migration and inflammation. Br J Pharmacol, v. 171, n. 24, p. 5491-506, Dec 2014. ISSN 1476-5381. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24571448 >. BISHOP, A. L.; HALL, A. Rho GTPases and their effector proteins. Biochem J, v. 348 Pt 2, p. 241-55, Jun 2000. ISSN 0264-6021. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10816416 >. BOUREUX, A. et al. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol, v. 24, n. 1, p. 203-16, Jan 2007. ISSN 0737-4038. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17035353 >. BURRIDGE, K.; WENNERBERG, K. Rho and Rac take center stage. Cell, v. 116, n. 2, p. 167-79, Jan 2004. ISSN 0092-8674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/14744429 >. CHEN, A. Y.; MYERS, J. N. Cancer of the oral cavity. Dis Mon, v. 47, n. 7, p. 275-361, Jul 2001. ISSN 0011-5029. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11477373 >. CHEN, W. et al. The role of the RhoA/Rho kinase pathway in angiogenesis and its potential value in prostate cancer (Review). Oncol Lett, v. 8, n. 5, p. 1907-1911, Nov 2014. ISSN 1792-1074. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25289078 >. CHIN, V. T. et al. Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities. Expert Rev Mol Med, v. 17, p. e17, Oct 2015. ISSN 1462-3994. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26507949 >. CHIOU, W. F. et al. Piperlactam S suppresses macrophage migration by impeding Factin polymerization and filopodia extension. Eur J Pharmacol, v. 458, n. 1-2, p. 217- 25, Jan 2003. ISSN 0014-2999. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12498929 >. CHOI, D. S. et al. SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II. Int J Cancer, v. 136, n. 5, p. E219-29, Mar 2015. ISSN 1097-0215. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25137150 >. CHOI, H. R. et al. Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis. Int J Oncol, v. 22, n. 2, p. 409-14, Feb 2003. ISSN 1019-6439. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12527941 >. CROFT, D. R.; OLSON, M. F. The Rho GTPase effector ROCK regulates cyclin A, cyclin D1, and p27Kip1 levels by distinct mechanisms. Mol Cell Biol, v. 26, n. 12, p. 4612-27, Jun 2006. ISSN 0270-7306. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/16738326 >. DAVID, M.; PETIT, D.; BERTOGLIO, J. Cell cycle regulation of Rho signaling pathways. Cell Cycle, v. 11, n. 16, p. 3003-10, Aug 2012. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22825247 >. DE TOLEDO, M. et al. Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity. PLoS One, v. 7, n. 11, p. e48344, 2012. ISSN 1932-6203. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23144867 >. DENG, L. et al. Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo. Cancer Biol Ther, v. 9, n. 11, p. 875-84, Jun 2010. ISSN 1555-8576. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20364104 >. ETIENNE-MANNEVILLE, S.; HALL, A. Rho GTPases in cell biology. Nature, v. 420, n. 6916, p. 629-35, Dec 2002. ISSN 0028-0836. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12478284 >. FARIED, A. et al. Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma. Ann Surg Oncol, v. 14, n. 12, p. 3593-601, Dec 2007. ISSN 1534-4681. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/17896152 >. FEHRENBACH, M. J.; HERRING, S. W. ANATOMIA ILUSTRADA DA CABEÇA E PESCOÇO ANATOMIA ILUSTRADA DA CABEÇA E PESCOÇO 2° edição: 2005. FENG, Y.; LOGRASSO, P. V. Rho kinase inhibitors: a patent review (2012 - 2013). Expert Opin Ther Pat, v. 24, n. 3, p. 295-307, Mar 2014. ISSN 1744-7674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24283930 >. FILHO, G. B. Bogliolo Patologia Geral. 3ª edição. Rio de Janeiro: Guanabara Koogan, 2004. FRITZ, G. et al. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer, v. 87, n. 6, p. 635-44, Sep 2002. ISSN 0007-0920. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12237774 >. FU, X. et al. The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle. FEBS Lett, v. 440, n. 1-2, p. 183-7, Nov 1998. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9862451 >. FUKUMOTO, Y. et al. Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart, v. 91, n. 3, p. 391-2, Mar 2005. ISSN 1468-201X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15710736 >. FUKUMOTO, Y.; SHIMOKAWA, H. Rho-kinase inhibitors. Handb Exp Pharmacol, v. 218, p. 351-63, 2013. ISSN 0171-2004. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24092347 >. GRAÑA, X.; REDDY, E. P. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene, v. 11, n. 2, p. 211-9, Jul 1995. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/7624138 >. GRINSPAN, D. Enfermedades de la bocca. Buenos Aires: 1980. GÓMEZ DEL PULGAR, T. et al. Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays, v. 27, n. 6, p. 602-13, Jun 2005. ISSN 0265-9247. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15892119 >. HALL, A. Rho GTPases and the control of cell behaviour. Biochem Soc Trans, v. 33, n. Pt 5, p. 891-5, Nov 2005. ISSN 0300-5127. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16246005 >. ______. Rho family GTPases. Biochem Soc Trans, v. 40, n. 6, p. 1378-82, Dec 2012. ISSN 1470-8752. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23176484 >. HANAHAN, D.; WEINBERG, R. A. Hallmarks of cancer: the next generation. Cell, v. 144, n. 5, p. 646-74, Mar 2011. ISSN 1097-4172. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/21376230 >. HANNA, S.; EL-SIBAI, M. Signaling networks of Rho GTPases in cell motility. Cell Signal, v. 25, n. 10, p. 1955-61, Oct 2013. ISSN 1873-3913. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23669310 >. HEASMAN, S. J.; RIDLEY, A. J. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol, v. 9, n. 9, p. 690-701, Sep 2008. ISSN 1471-0080. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/18719708 >. HIROSE, M. et al. Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J Cell Biol, v. 141, n. 7, p. 1625-36, Jun 1998. ISSN 0021-9525. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9647654 >. HUANG, H. et al. Metabolic actions of Rho-kinase in periphery and brain. Trends Endocrinol Metab, v. 24, n. 10, p. 506-14, Oct 2013. ISSN 1879-3061. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23938132 >. INABA, N. et al. Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells. Anticancer Res, v. 30, n. 9, p. 3509-14, Sep 2010. ISSN 1791-7530. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20944130 >. INCA. Estimativa 2016: Incidência de câncer no Brasil. Rio de Janeiro 2016. ITOH, K. et al. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med, v. 5, n. 2, p. 221-5, Feb 1999. ISSN 1078-8956. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9930872 >. IZAWA, I. et al. Possible involvement of the inactivation of the Rho-Rho-kinase pathway in oncogenic Ras-induced transformation. Oncogene, v. 17, n. 22, p. 2863-71, Dec 1998. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9879992 >. JAFFE, A. B.; HALL, A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol, v. 21, p. 247-69, 2005. ISSN 1081-0706. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16212495 >. JEONG, K. J. et al. The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene, v. 31, n. 39, p. 4279-89, Sep 2012. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22249252 >. JULIAN, L.; OLSON, M. F. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases, v. 5, p. e29846, 2014. ISSN 2154- 1256. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25010901 >. JUNQUEIRA, L. C.; CARNEIRO, J. Biologia Celular e Molecular. 8ª ed. 2005. KAMAI, T. et al. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res, v. 9, n. 7, p. 2632-41, Jul 2003. ISSN 1078-0432. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12855641 >. KARLSSON, R. et al. Rho GTPase function in tumorigenesis. Biochim Biophys Acta, v. 1796, n. 2, p. 91-8, Dec 2009. ISSN 0006-3002. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/19327386 >. KATCHBURIAN, E.; ARANA, V. Histologia e Embriologia Oral 3a ed. Rio de Janeiro: 2012. 372. KIMURA, K. et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science, v. 273, n. 5272, p. 245-8, Jul 1996. ISSN 0036-8075. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/8662509 >. KITAJO, H. et al. Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells. Oncol Rep, v. 10, n. 5, p. 1351-6, 2003 Sep-Oct 2003. ISSN 1021-335X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12883706 >. KJOLLER, L.; HALL, A. Signaling to Rho GTPases. Exp Cell Res, v. 253, n. 1, p. 166-79, Nov 1999. ISSN 0014-4827. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10579921 >. KLAGES, B. et al. Activation of G12/G13 results in shape change and Rho/Rho-kinasemediated myosin light chain phosphorylation in mouse platelets. J Cell Biol, v. 144, n. 4, p. 745-54, Feb 1999. ISSN 0021-9525. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10037795 >. KLEER, C. G. et al. RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck. Clin Cancer Res, v. 12, n. 15, p. 4485-90, Aug 2006. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16899593 >. KLEIN, E. A. et al. NFkappaB-independent signaling to the cyclin D1 gene by Rac. Cell Cycle, v. 6, n. 9, p. 1115-21, May 2007. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/17426454 >. KNIPE, R. S.; TAGER, A. M.; LIAO, J. K. The Rho kinases: critical mediators of multiple profibrotic processes and rational targets for new therapies for pulmonary fibrosis. Pharmacol Rev, v. 67, n. 1, p. 103-17, 2015. ISSN 1521-0081. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25395505 >. KOSAKO, H. et al. Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow. Oncogene, v. 19, n. 52, p. 6059-64, Dec 2000. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11146558 >. KROISS, A. et al. Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1 and ROCK2. Oncogene, v. 34, n. 22, p. 2846-55, May 2015. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25065599 >. KUMAR, V.; ABBAS, A. K.; FAUSTO, N. Robbins e Cotran: Patologia: Bases Patológicas das Doenças. 7° Edição Rio de Janeiro: 2005. KUROPKAT, C. et al. Proliferation marker Ki-S11--a prognostic indicator for squamous cell carcinoma of the hypopharynx. Virchows Arch, v. 435, n. 6, p. 590-5, Dec 1999. ISSN 0945-6317. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10628801 >. KUWAHARA, K. et al. The effects of the selective ROCK inhibitor, Y27632, on ET-1- induced hypertrophic response in neonatal rat cardiac myocytes--possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett, v. 452, n. 3, p. 314-8, Jun 1999. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10386613 >. KÜHN, S.; GEYER, M. Formins as effector proteins of Rho GTPases. Small GTPases, v. 5, p. e29513, 2014. ISSN 2154-1256. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24914801 >. KÜMPER, S. et al. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis. Elife, v. 5, p. e12994, Jan 2016. ISSN 2050- 084X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26765561 >. LAI, S. Y. et al. Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma. Oral Oncol, v. 44, n. 7, p. 683-8, Jul 2008. ISSN 1368- 8375. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17996485 >. LEETHANAKUL, C. et al. Distinct pattern of expression of differentiation and growthrelated genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene, v. 19, n. 28, p. 3220-4, Jun 2000. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10918578 >. LI, M. et al. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease. PLoS One, v. 8, n. 2, p. e56026, 2013. ISSN 1932-6203. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23409115 >. LIAO, Y. C. et al. Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene, v. 31, n. 25, p. 3086-97, Jun 2012. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22002306 >. LIU, S. et al. Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res, v. 69, n. 22, p. 8742-51, Nov 2009. ISSN 1538- 7445. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19887617 >. LIU, S. Y. et al. Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma. J Oral Maxillofac Surg, v. 62, n. 6, p. 702-7, Jun 2004. ISSN 0278-2391. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15170282 >. LÓPEZ, R. V. et al. Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection. Cancer Causes Control, v. 25, n. 4, p. 461-71, Apr 2014. ISSN 1573-7225. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24474236 >. MA, Z. et al. p66(Shc) restrains Ras hyperactivation and suppresses metastatic behavior. Oncogene, v. 29, n. 41, p. 5559-67, Oct 2010. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20676142 >. MADDALA, R. et al. Growth factor induced activation of Rho and Rac GTPases and actin cytoskeletal reorganization in human lens epithelial cells. Mol Vis, v. 9, p. 329-36, Jul 2003. ISSN 1090-0535. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12876554 >. MALUMBRES, M.; BARBACID, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer, v. 9, n. 3, p. 153-66, Mar 2009. ISSN 1474-1768. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19238148 >. MALUMBRES, M. et al. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol Sci, v. 29, n. 1, p. 16-21, Jan 2008. ISSN 0165-6147. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/18054800 >. MAMMOTO, A. et al. Role of RhoA, mDia, and ROCK in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition. J Biol Chem, v. 279, n. 25, p. 26323-30, Jun 2004. ISSN 0021-9258. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15096506 >. MASSAGUÉ, J. G1 cell-cycle control and cancer. Nature, v. 432, n. 7015, p. 298-306, Nov 2004. ISSN 1476-4687. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15549091 >. MASSANO, J. et al. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, v. 102, n. 1, p. 67-76, Jul 2006. ISSN 1528-395X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16831675 >. MATSUMURA, F. Regulation of myosin II during cytokinesis in higher eukaryotes. Trends Cell Biol, v. 15, n. 7, p. 371-7, Jul 2005. ISSN 0962-8924. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15935670 >. MAZIERES, J. et al. Loss of RhoB expression in human lung cancer progression. Clin Cancer Res, v. 10, n. 8, p. 2742-50, Apr 2004. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15102679 >. MERAJVER, S. D.; USMANI, S. Z. Multifaceted role of Rho proteins in angiogenesis. J Mammary Gland Biol Neoplasia, v. 10, n. 4, p. 291-8, Oct 2005. ISSN 1083-3021. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16900393 >. MERTSCH, S.; THANOS, S. Opposing signaling of ROCK1 and ROCK2 determines the switching of substrate specificity and the mode of migration of glioblastoma cells. Mol Neurobiol, v. 49, n. 2, p. 900-15, Apr 2014. ISSN 1559-1182. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24170433 >. METTOUCHI, A. et al. Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Mol Cell, v. 8, n. 1, p. 115-27, Jul 2001. ISSN 1097- 2765. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11511365 >. MIKURIYA, Y. et al. Fatty liver creates a pro-metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells. Int J Cancer, v. 136, n. 4, p. E3-13, Feb 2015. ISSN 1097-0215. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25053237 >. MINETA, H. et al. Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma. Cancer, v. 85, n. 5, p. 1011-7, Mar 1999. ISSN 0008-543X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10091782 >. MISHRA, A. K.; LAMBRIGHT, D. G. Invited review: Small GTPases and their GAPs. Biopolymers, v. 105, n. 8, p. 431-48, Aug 2016. ISSN 1097-0282. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26972107 >. MONTALVO, J. et al. ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression. Curr Mol Med, v. 13, n. 1, p. 205-19, Jan 2013. ISSN 1875-5666. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22934846 >. MONTORO, J. R. et al. Prognostic factors in squamous cell carcinoma of the oral cavity. Braz J Otorhinolaryngol, v. 74, n. 6, p. 861-6, 2008 Nov-Dec 2008. ISSN 1808-8694. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/19582342 >. MOREIRA CARBONI, S. E. S. et al. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, v. 26, n. 9, p. 923-30, Oct 2015. ISSN 1473-5741. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26181228 >. MOREIRA CARBONI, S. S. et al. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, Jul 2015. ISSN 1473-5741. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26181228 >. MORGAN-FISHER, M.; WEWER, U. M.; YONEDA, A. Regulation of ROCK activity in cancer. J Histochem Cytochem, v. 61, n. 3, p. 185-98, Mar 2013. ISSN 1551-5044. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23204112 >. NANCI, A. Ten Cate's Oral Histology Development, Structure and Function 8 a edição. Montreal: 2013. 398. NIGGLI, V. Rho-kinase in human neutrophils: a role in signalling for myosin light chain phosphorylation and cell migration. FEBS Lett, v. 445, n. 1, p. 69-72, Feb 1999. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10069376 >. NILIUS, B. et al. Role of Rho and Rho kinase in the activation of volume-regulated anion channels in bovine endothelial cells. J Physiol, v. 516 ( Pt 1), p. 67-74, Apr 1999. ISSN 0022-3751. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10066923 >. NOBES, C.; MARSH, M. Dendritic cells: new roles for Cdc42 and Rac in antigen uptake? Curr Biol, v. 10, n. 20, p. R739-41, Oct 2000. ISSN 0960-9822. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11069097 >. OHASHI, K. et al. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem, v. 275, n. 5, p. 3577-82, Feb 2000. ISSN 0021-9258. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10652353 >. OLSON, M. F. Applications for ROCK kinase inhibition. Curr Opin Cell Biol, v. 20, n. 2, p. 242-8, Apr 2008. ISSN 0955-0674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/18282695 >. PAN, P. et al. Advances in the development of Rho-associated protein kinase (ROCK) inhibitors. Drug Discov Today, v. 18, n. 23-24, p. 1323-33, Dec 2013. ISSN 1878-5832. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24076262 >. PENG, J. et al. ROCK cooperated with ET-1 to induce epithelial to mesenchymal transition through SLUG in human ovarian cancer cells. Biosci Biotechnol Biochem, v. 76, n. 1, p. 42-7, 2012. ISSN 1347-6947. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22232246 >. PERNIS, A. B. et al. Rho Kinases in Autoimmune Diseases. Annu Rev Med, v. 67, p. 355- 74, 2016. ISSN 1545-326X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26768244 >. PINHEIRO, N. M. Papel Funcional das GTPases Rho na proliferação e Diferenciação Celular em Carcinoma Epidermóide Oral. 2010. 109 Universidade Federal do Triângulo Mineiro POLLARD, T., D.; EARNSHAW, W. C. Biologia Celular. 2006. PRENDERGAST, G. C. Actin' up: RhoB in cancer and apoptosis. Nat Rev Cancer, v. 1, n. 2, p. 162-8, Nov 2001. ISSN 1474-175X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11905808 >. PULTE, D.; BRENNER, H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist, v. 15, n. 9, p. 994-1001, 2010. ISSN 1549-490X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20798198 >. RAISOVA, M. et al. Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release. FEBS Lett, v. 473, n. 1, p. 27-32, May 2000. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10802053 >. REYMOND, N. et al. RhoC and ROCKs regulate cancer cell interactions with endothelial cells. Mol Oncol, v. 9, n. 6, p. 1043-55, Jun 2015. ISSN 1878-0261. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25677806 >. RIDLEY, A. J. Rho GTPase signalling in cell migration. Curr Opin Cell Biol, v. 36, p. 103- 112, Sep 2015. ISSN 1879-0410. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26363959 >. ROCHELLE, T. et al. p210bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1. FASEB J, v. 27, n. 1, p. 123-34, Jan 2013. ISSN 1530-6860. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23047898 >. SAHAI, E. et al. Transformation mediated by RhoA requires activity of ROCK kinases. Curr Biol, v. 9, n. 3, p. 136-45, Feb 1999. ISSN 0960-9822. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10021386 >. SAMUEL, M. S. et al. Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell, v. 19, n. 6, p. 776-91, Jun 2011. ISSN 1878-3686. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/21665151 >. SASAKI, Y.; SUZUKI, M.; HIDAKA, H. The novel and specific Rho-kinase inhibitor (S)-(+)- 2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine as a probing molecule for Rho-kinase-involved pathway. Pharmacol Ther, v. 93, n. 2-3, p. 225-32, 2002 FebMar 2002. ISSN 0163-7258. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12191614 >. SAUTER, E. R. et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res, v. 62, n. 11, p. 3200-6, Jun 2002. ISSN 0008-5472. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12036934 >. SAWADA, N.; LIAO, J. K. Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis. Antioxid Redox Signal, v. 20, n. 8, p. 1251-67, Mar 2014. ISSN 1557-7716. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23919640 >. SCHMITZ, A. A. et al. Rho GTPases: signaling, migration, and invasion. Exp Cell Res, v. 261, n. 1, p. 1-12, Nov 2000. ISSN 0014-4827. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11082269 >. SCHNELZER, A. et al. Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene, v. 19, n. 26, p. 3013-20, Jun 2000. ISSN 0950-9232. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10871853 >. SCHOFIELD, A. V.; BERNARD, O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol, v. 48, n. 4, p. 301-16, 2013 Jul-Aug 2013. ISSN 1549-7798. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23601011 >. SCIUBBA, J. J. Oral cancer and its detection. History-taking and the diagnostic phase of management. J Am Dent Assoc, v. 132 Suppl, p. 12S-18S, Nov 2001. ISSN 0002-8177. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11803647 >. SCULLY, C.; BAGAN, J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis, v. 15, n. 6, p. 388-99, Sep 2009. ISSN 1601-0825. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19371401 >. SEASHOLTZ, T. M. et al. Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration. Circ Res, v. 84, n. 10, p. 1186-93, May 1999. ISSN 0009-7330. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10347093 >. SEBBAGH, M. et al. Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner. J Exp Med, v. 201, n. 3, p. 465- 71, Feb 2005. ISSN 0022-1007. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15699075 >. SHI, J. et al. Dissecting the roles of ROCK isoforms in stress-induced cell detachment. Cell Cycle, v. 12, n. 10, p. 1492-500, May 2013. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23598717 >. SHI, J.; WEI, L. Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. J Cardiovasc Pharmacol, v. 62, n. 4, p. 341-54, Oct 2013. ISSN 1533- 4023. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23921309 >. SQUIER, C. A.; KREMER, M. J. Biology of oral mucosa and esophagus. J Natl Cancer Inst Monogr, n. 29, p. 7-15, 2001. ISSN 1052-6773. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11694559 >. SUN, K. et al. Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in MCF7 breast cancer cells. Clin Exp Med, v. 16, n. 1, p. 37-47, Feb 2016. ISSN 1591-9528. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25596714 >. TAKAI, Y.; SASAKI, T.; MATOZAKI, T. Small GTP-binding proteins. Physiol Rev, v. 81, n. 1, p. 153-208, Jan 2001. ISSN 0031-9333. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11152757 >. TAKEBA, Y. et al. The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells. Cancer Chemother Pharmacol, v. 69, n. 6, p. 1545-55, Jun 2012. ISSN 1432-0843. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/22481618 >. TSELIOU, M. et al. The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells. Cell Physiol Biochem, v. 38, n. 1, p. 94-109, 2016. ISSN 1421-9778. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26741994 >. UEHATA, M. et al. Calcium sensitization of smooth muscle mediated by a Rhoassociated protein kinase in hypertension. Nature, v. 389, n. 6654, p. 990-4, Oct 1997. ISSN 0028-0836. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9353125 >. VAN AELST, L.; D'SOUZA-SCHOREY, C. Rho GTPases and signaling networks. Genes Dev, v. 11, n. 18, p. 2295-322, Sep 1997. ISSN 0890-9369. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/9308960 >. VARGAS-FERREIRA, F. et al. Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: a brief approach. Braz Dent J, v. 23, n. 5, p. 586-90, 2012. ISSN 1806-4760. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23306239 >. VEGA, F. M.; RIDLEY, A. J. Rho GTPases in cancer cell biology. FEBS Lett, v. 582, n. 14, p. 2093-101, Jun 2008. ISSN 0014-5793. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/18460342 >. ______. The RhoB small GTPase in physiology and disease. Small GTPases, p. 1-10, Nov 2016. ISSN 2154-1256. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/27875099 >. VIGIL, D. et al. ROCK1 and ROCK2 are required for non-small cell lung cancer anchorage-independent growth and invasion. Cancer Res, v. 72, n. 20, p. 5338-47, Oct 2012. ISSN 1538-7445. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22942252 >. VISHNUBHOTLA, R. et al. Treatment with Y-27632, a ROCK Inhibitor, Increases the Proinvasive Nature of SW620 Cells on 3D Collagen Type 1 Matrix. Int J Cell Biol, v. 2012, p. 259142, 2012. ISSN 1687-8884. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22690219 >. WANG, H. et al. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo. J Exp Clin Cancer Res, v. 29, p. 123, Sep 2010. ISSN 1756-9966. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20828398 >. WANG, J. et al. The effect of ROCK-1 activity change on the adhesive and invasive ability of Y79 retinoblastoma cells. BMC Cancer, v. 14, p. 89, Feb 2014. ISSN 1471- 2407. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24528629 >. WANG, Z. M. et al. ROCK inhibitor Y-27632 inhibits the growth, migration, and invasion of Tca8113 and CAL-27 cells in tongue squamous cell carcinoma. Tumour Biol, v. 37, n. 3, p. 3757-64, Mar 2016. ISSN 1423-0380. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26468018 >. WATZLAWICK, R. et al. Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis. JAMA Neurol, v. 71, n. 1, p. 91-9, Jan 2014. ISSN 2168-6157. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24297045 >. WEI, L. et al. Novel Insights into the Roles of Rho Kinase in Cancer. Arch Immunol Ther Exp (Warsz), v. 64, n. 4, p. 259-78, Aug 2016. ISSN 1661-4917. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26725045 >. WHEELER, A. P.; RIDLEY, A. J. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Exp Cell Res, v. 301, n. 1, p. 43-9, Nov 2004. ISSN 0014-4827. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15501444 >. WONG, S. Y. et al. Constitutive activation of myosin-dependent contractility sensitizes glioma tumor-initiating cells to mechanical inputs and reduces tissue invasion. Cancer Res, v. 75, n. 6, p. 1113-22, Mar 2015. ISSN 1538-7445. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25634210 >. XIAO, J. W. et al. Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects. Circ J, v. 79, n. 6, p. 1342-8, 2015. ISSN 1347-4820. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/25797071 >. XU, N. et al. Fasudil inhibits proliferation and collagen synthesis and induces apoptosis of human fibroblasts derived from urethral scar via the Rho/ROCK signaling pathway. Am J Transl Res, v. 9, n. 3, p. 1317-1325, 2017. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/28386357 >. XUE, Z. W. et al. Rho-associated coiled kinase inhibitor Y-27632 promotes neuronallike differentiation of adult human adipose tissue-derived stem cells. Chin Med J (Engl), v. 125, n. 18, p. 3332-5, Sep 2012. ISSN 0366-6999. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22964332 >. YAN, G. et al. Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer. Acta Biochim Biophys Sin (Shanghai), v. 46, n. 8, p. 682-90, Aug 2014. ISSN 1745-7270. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25001480 >. YANG, S.; KIM, H. M. ROCK inhibition activates MCF-7 cells. PLoS One, v. 9, n. 2, p. e88489, 2014. ISSN 1932-6203. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24523903 >. YANG, X. et al. Effect of fasudil on growth, adhesion, invasion, and migration of 95D lung carcinoma cells in vitro. Can J Physiol Pharmacol, v. 88, n. 9, p. 874-9, Sep 2010. ISSN 1205-7541. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20921973 >. YOSHIDA, A. et al. VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells. Biol Open, v. 4, n. 9, p. 1063-76, Jul 2015. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26209534>. YOSHII, A. et al. Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization. Am J Respir Cell Mol Biol, v. 20, n. 6, p. 1190-200, Jun 1999. ISSN 1044-1549. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10340938 >. ZHANG, H. Z. et al. Expression of G3BP and RhoC in esophageal squamous carcinoma and their effect on prognosis. World J Gastroenterol, v. 13, n. 30, p. 4126-30, Aug 2007. ISSN 1007-9327. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17696235 >. ZHANG, J. et al. Overexpression of ROCK1 and ROCK2 inhibits human laryngeal squamous cell carcinoma. Int J Clin Exp Pathol, v. 8, n. 1, p. 244-51, 2015. ISSN 1936- 2625. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25755711 >. ZHANG, S. et al. RhoA regulates G1-S progression of gastric cancer cells by modulation of multiple INK4 family tumor suppressors. Mol Cancer Res, v. 7, n. 4, p. 570-80, Apr 2009. ISSN 1541-7786. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19372585 >. ZHANG, Z. et al. Fasudil inhibits lung carcinoma-conditioned endothelial cell viability and migration. Oncol Rep, v. 27, n. 5, p. 1561-6, May 2012. ISSN 1791-2431. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22344855 >. ZHU, F. et al. Rho kinase inhibitor fasudil suppresses migration and invasion though down-regulating the expression of VEGF in lung cancer cell line A549. Med Oncol, v. 28, n. 2, p. 565-71, Jun 2011. ISSN 1559-131X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20300976>.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-07-23T04:00:16Zoai:bdtd.uftm.edu.br:tede/781Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-07-23T04:00:16Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
dc.title.none.fl_str_mv Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
title Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
spellingShingle Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
BORGES, Guilherme Henrique
Carcinoma de epidermoide oral.
HA-1077.
Proliferação celular.
ROCKs.
Y-27632.
Oral squamous cell carcinoma.
HA-1077.
Cell proliferation.
ROCKs.
Y-27632.
Morfologia
Citologia e Biologia Celular
title_short Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
title_full Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
title_fullStr Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
title_full_unstemmed Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
title_sort Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro
author BORGES, Guilherme Henrique
author_facet BORGES, Guilherme Henrique
author_role author
dc.contributor.none.fl_str_mv CREMA, Virgínia Oliveira
66127211620
http://lattes.cnpq.br/2599388555203811
dc.contributor.author.fl_str_mv BORGES, Guilherme Henrique
dc.subject.por.fl_str_mv Carcinoma de epidermoide oral.
HA-1077.
Proliferação celular.
ROCKs.
Y-27632.
Oral squamous cell carcinoma.
HA-1077.
Cell proliferation.
ROCKs.
Y-27632.
Morfologia
Citologia e Biologia Celular
topic Carcinoma de epidermoide oral.
HA-1077.
Proliferação celular.
ROCKs.
Y-27632.
Oral squamous cell carcinoma.
HA-1077.
Cell proliferation.
ROCKs.
Y-27632.
Morfologia
Citologia e Biologia Celular
description O carcinoma epidermoide oral é uma neoplasia epitelial responsável pela maioria das lesões malignas que acometem a região de cabeça e pescoço. O e o Y-27632 são inibidores das ROCKs, que são efetoras das GTPases Rho, e estão associadas à patogênese e progressão de tumores humanos. Este estudo visou avaliar o papel funcional das ROCKs na regulação da proliferação de células SCC-4 de carcinoma epidermoide oral in vitro. Foram quantificadas as células SCC-4 de carcinoma epidermoide oral controle e tratadas com HA-1077 (25, 50 e 100 μM) por 6 e 24 horas; e HA-1077 (25, 50 e 100 μM), HA-1077 50 µM e/ou Y-27632 30 µM por 6 horas, em ensaios de incorporação de BrdU e imunoexpressão de KI-67. Foi considerado significante p<0,05. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM) que incorporaram BrdU foi significativamente menor que o de células controle em 6 horas [F(3,11) = 107,461, p<0,0001] e 24 horas [F(3,11) = 167,433, p<0,0001], de modo dose dependente. O número de células SCC-4 tratadas com HA-1077 (25, 50 e 100 μM), HA- 1077 50 µM e/ou Y-27632, por 6 horas, que incorporaram BrdU [F(5,17) = 443,818, p<0,0001], e o número que imunoexpressaram KI-67, também, foi significativamente menor [F(5,17) = 192,595, p<0,0001], que o de células controle. Os resultados obtidos sugerem que as proteínas ROCKs desempenham um papel funcional importante na regulação da proliferação celular em carcinoma epidermoide oral, uma vez que o HA-1077 e/ou o Y- 27632, inibidores de ROCKs, têm um efeito inibitório sobre a proliferação de células SCC-4.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-22
2019-07-22T14:25:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv BORGES, Guilherme Henrique. Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro. 2017. 74f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2017.
http://bdtd.uftm.edu.br/handle/tede/781
identifier_str_mv BORGES, Guilherme Henrique. Papel funcional das rocks sobre a proliferação de células de carcinoma epidermoide oral in vitro. 2017. 74f. Dissertação (Mestrado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2017.
url http://bdtd.uftm.edu.br/handle/tede/781
dc.language.iso.fl_str_mv por
language por
dc.relation.none.fl_str_mv ABE, H. et al. The Rho-kinase inhibitor HA-1077 suppresses proliferation/migration and induces apoptosis of urothelial cancer cells. BMC Cancer, v. 14, p. 412, 2014. ISSN 1471-2407. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24908363 >. ADNANE, J. et al. Suppression of rho B expression in invasive carcinoma from head and neck cancer patients. Clin Cancer Res, v. 8, n. 7, p. 2225-32, Jul 2002. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12114424 >. ALBERTS, B. E. A. Molecular Biology of The Cell 5a. 2008. 1268. AMANO, M.; NAKAYAMA, M.; KAIBUCHI, K. Rho-kinase/ROCK: A key regulator of the cytoskeleton and cell polarity. Cytoskeleton (Hoboken), v. 67, n. 9, p. 545-54, Sep 2010. ISSN 1949-3592. Disponível em: <http://www.ncbi.nlm.nih.gov/pubmed/20803696 >. AMANO, M. et al. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase. PLoS One, v. 5, n. 1, p. e8704, Jan 2010. ISSN 1932- 6203. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20090853 >. ASANO, T. et al. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther, v. 241, n. 3, p. 1033-40, Jun 1987. ISSN 0022-3565. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/3598899 >. BAGAN, J. V.; SCULLY, C. Recent advances in Oral Oncology 2007: epidemiology, aetiopathogenesis, diagnosis and prognostication. Oral Oncol, v. 44, n. 2, p. 103-8, Feb 2008. ISSN 1368-8375. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/18252251 >. ______. Recent advances in Oral Oncology 2008; squamous cell carcinoma aetiopathogenesis and experimental studies. Oral Oncol, v. 45, n. 7, p. e45-8, Jul 2009. ISSN 1879-0593. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19196543 >. BARNES, L.; EVERSON, J. W.; REICHART, P. World health organization classification of tumours pathology and genetics of head and neck tumours. 2005. BIRO, M.; MUNOZ, M. A.; WENINGER, W. Targeting Rho-GTPases in immune cell migration and inflammation. Br J Pharmacol, v. 171, n. 24, p. 5491-506, Dec 2014. ISSN 1476-5381. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24571448 >. BISHOP, A. L.; HALL, A. Rho GTPases and their effector proteins. Biochem J, v. 348 Pt 2, p. 241-55, Jun 2000. ISSN 0264-6021. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10816416 >. BOUREUX, A. et al. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol, v. 24, n. 1, p. 203-16, Jan 2007. ISSN 0737-4038. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17035353 >. BURRIDGE, K.; WENNERBERG, K. Rho and Rac take center stage. Cell, v. 116, n. 2, p. 167-79, Jan 2004. ISSN 0092-8674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/14744429 >. CHEN, A. Y.; MYERS, J. N. Cancer of the oral cavity. Dis Mon, v. 47, n. 7, p. 275-361, Jul 2001. ISSN 0011-5029. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11477373 >. CHEN, W. et al. The role of the RhoA/Rho kinase pathway in angiogenesis and its potential value in prostate cancer (Review). Oncol Lett, v. 8, n. 5, p. 1907-1911, Nov 2014. ISSN 1792-1074. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25289078 >. CHIN, V. T. et al. Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities. Expert Rev Mol Med, v. 17, p. e17, Oct 2015. ISSN 1462-3994. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26507949 >. CHIOU, W. F. et al. Piperlactam S suppresses macrophage migration by impeding Factin polymerization and filopodia extension. Eur J Pharmacol, v. 458, n. 1-2, p. 217- 25, Jan 2003. ISSN 0014-2999. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12498929 >. CHOI, D. S. et al. SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II. Int J Cancer, v. 136, n. 5, p. E219-29, Mar 2015. ISSN 1097-0215. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25137150 >. CHOI, H. R. et al. Differential expressions of cyclin-dependent kinase inhibitors (p27 and p21) and their relation to p53 and Ki-67 in oral squamous tumorigenesis. Int J Oncol, v. 22, n. 2, p. 409-14, Feb 2003. ISSN 1019-6439. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12527941 >. CROFT, D. R.; OLSON, M. F. The Rho GTPase effector ROCK regulates cyclin A, cyclin D1, and p27Kip1 levels by distinct mechanisms. Mol Cell Biol, v. 26, n. 12, p. 4612-27, Jun 2006. ISSN 0270-7306. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/16738326 >. DAVID, M.; PETIT, D.; BERTOGLIO, J. Cell cycle regulation of Rho signaling pathways. Cell Cycle, v. 11, n. 16, p. 3003-10, Aug 2012. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22825247 >. DE TOLEDO, M. et al. Cooperative anti-invasive effect of Cdc42/Rac1 activation and ROCK inhibition in SW620 colorectal cancer cells with elevated blebbing activity. PLoS One, v. 7, n. 11, p. e48344, 2012. ISSN 1932-6203. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23144867 >. DENG, L. et al. Rho-kinase inhibitor, fasudil, suppresses glioblastoma cell line progression in vitro and in vivo. Cancer Biol Ther, v. 9, n. 11, p. 875-84, Jun 2010. ISSN 1555-8576. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20364104 >. ETIENNE-MANNEVILLE, S.; HALL, A. Rho GTPases in cell biology. Nature, v. 420, n. 6916, p. 629-35, Dec 2002. ISSN 0028-0836. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12478284 >. FARIED, A. et al. Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma. Ann Surg Oncol, v. 14, n. 12, p. 3593-601, Dec 2007. ISSN 1534-4681. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/17896152 >. FEHRENBACH, M. J.; HERRING, S. W. ANATOMIA ILUSTRADA DA CABEÇA E PESCOÇO ANATOMIA ILUSTRADA DA CABEÇA E PESCOÇO 2° edição: 2005. FENG, Y.; LOGRASSO, P. V. Rho kinase inhibitors: a patent review (2012 - 2013). Expert Opin Ther Pat, v. 24, n. 3, p. 295-307, Mar 2014. ISSN 1744-7674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24283930 >. FILHO, G. B. Bogliolo Patologia Geral. 3ª edição. Rio de Janeiro: Guanabara Koogan, 2004. FRITZ, G. et al. Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters. Br J Cancer, v. 87, n. 6, p. 635-44, Sep 2002. ISSN 0007-0920. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12237774 >. FU, X. et al. The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgammaS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle. FEBS Lett, v. 440, n. 1-2, p. 183-7, Nov 1998. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9862451 >. FUKUMOTO, Y. et al. Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart, v. 91, n. 3, p. 391-2, Mar 2005. ISSN 1468-201X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15710736 >. FUKUMOTO, Y.; SHIMOKAWA, H. Rho-kinase inhibitors. Handb Exp Pharmacol, v. 218, p. 351-63, 2013. ISSN 0171-2004. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24092347 >. GRAÑA, X.; REDDY, E. P. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene, v. 11, n. 2, p. 211-9, Jul 1995. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/7624138 >. GRINSPAN, D. Enfermedades de la bocca. Buenos Aires: 1980. GÓMEZ DEL PULGAR, T. et al. Rho GTPase expression in tumourigenesis: evidence for a significant link. Bioessays, v. 27, n. 6, p. 602-13, Jun 2005. ISSN 0265-9247. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15892119 >. HALL, A. Rho GTPases and the control of cell behaviour. Biochem Soc Trans, v. 33, n. Pt 5, p. 891-5, Nov 2005. ISSN 0300-5127. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16246005 >. ______. Rho family GTPases. Biochem Soc Trans, v. 40, n. 6, p. 1378-82, Dec 2012. ISSN 1470-8752. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23176484 >. HANAHAN, D.; WEINBERG, R. A. Hallmarks of cancer: the next generation. Cell, v. 144, n. 5, p. 646-74, Mar 2011. ISSN 1097-4172. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/21376230 >. HANNA, S.; EL-SIBAI, M. Signaling networks of Rho GTPases in cell motility. Cell Signal, v. 25, n. 10, p. 1955-61, Oct 2013. ISSN 1873-3913. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23669310 >. HEASMAN, S. J.; RIDLEY, A. J. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol, v. 9, n. 9, p. 690-701, Sep 2008. ISSN 1471-0080. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/18719708 >. HIROSE, M. et al. Molecular dissection of the Rho-associated protein kinase (p160ROCK)-regulated neurite remodeling in neuroblastoma N1E-115 cells. J Cell Biol, v. 141, n. 7, p. 1625-36, Jun 1998. ISSN 0021-9525. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9647654 >. HUANG, H. et al. Metabolic actions of Rho-kinase in periphery and brain. Trends Endocrinol Metab, v. 24, n. 10, p. 506-14, Oct 2013. ISSN 1879-3061. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23938132 >. INABA, N. et al. Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells. Anticancer Res, v. 30, n. 9, p. 3509-14, Sep 2010. ISSN 1791-7530. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20944130 >. INCA. Estimativa 2016: Incidência de câncer no Brasil. Rio de Janeiro 2016. ITOH, K. et al. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med, v. 5, n. 2, p. 221-5, Feb 1999. ISSN 1078-8956. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9930872 >. IZAWA, I. et al. Possible involvement of the inactivation of the Rho-Rho-kinase pathway in oncogenic Ras-induced transformation. Oncogene, v. 17, n. 22, p. 2863-71, Dec 1998. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9879992 >. JAFFE, A. B.; HALL, A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol, v. 21, p. 247-69, 2005. ISSN 1081-0706. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16212495 >. JEONG, K. J. et al. The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene, v. 31, n. 39, p. 4279-89, Sep 2012. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22249252 >. JULIAN, L.; OLSON, M. F. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases, v. 5, p. e29846, 2014. ISSN 2154- 1256. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25010901 >. JUNQUEIRA, L. C.; CARNEIRO, J. Biologia Celular e Molecular. 8ª ed. 2005. KAMAI, T. et al. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res, v. 9, n. 7, p. 2632-41, Jul 2003. ISSN 1078-0432. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12855641 >. KARLSSON, R. et al. Rho GTPase function in tumorigenesis. Biochim Biophys Acta, v. 1796, n. 2, p. 91-8, Dec 2009. ISSN 0006-3002. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/19327386 >. KATCHBURIAN, E.; ARANA, V. Histologia e Embriologia Oral 3a ed. Rio de Janeiro: 2012. 372. KIMURA, K. et al. Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase). Science, v. 273, n. 5272, p. 245-8, Jul 1996. ISSN 0036-8075. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/8662509 >. KITAJO, H. et al. Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells. Oncol Rep, v. 10, n. 5, p. 1351-6, 2003 Sep-Oct 2003. ISSN 1021-335X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12883706 >. KJOLLER, L.; HALL, A. Signaling to Rho GTPases. Exp Cell Res, v. 253, n. 1, p. 166-79, Nov 1999. ISSN 0014-4827. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10579921 >. KLAGES, B. et al. Activation of G12/G13 results in shape change and Rho/Rho-kinasemediated myosin light chain phosphorylation in mouse platelets. J Cell Biol, v. 144, n. 4, p. 745-54, Feb 1999. ISSN 0021-9525. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10037795 >. KLEER, C. G. et al. RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck. Clin Cancer Res, v. 12, n. 15, p. 4485-90, Aug 2006. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16899593 >. KLEIN, E. A. et al. NFkappaB-independent signaling to the cyclin D1 gene by Rac. Cell Cycle, v. 6, n. 9, p. 1115-21, May 2007. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/17426454 >. KNIPE, R. S.; TAGER, A. M.; LIAO, J. K. The Rho kinases: critical mediators of multiple profibrotic processes and rational targets for new therapies for pulmonary fibrosis. Pharmacol Rev, v. 67, n. 1, p. 103-17, 2015. ISSN 1521-0081. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25395505 >. KOSAKO, H. et al. Rho-kinase/ROCK is involved in cytokinesis through the phosphorylation of myosin light chain and not ezrin/radixin/moesin proteins at the cleavage furrow. Oncogene, v. 19, n. 52, p. 6059-64, Dec 2000. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11146558 >. KROISS, A. et al. Androgen-regulated microRNA-135a decreases prostate cancer cell migration and invasion through downregulating ROCK1 and ROCK2. Oncogene, v. 34, n. 22, p. 2846-55, May 2015. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25065599 >. KUMAR, V.; ABBAS, A. K.; FAUSTO, N. Robbins e Cotran: Patologia: Bases Patológicas das Doenças. 7° Edição Rio de Janeiro: 2005. KUROPKAT, C. et al. Proliferation marker Ki-S11--a prognostic indicator for squamous cell carcinoma of the hypopharynx. Virchows Arch, v. 435, n. 6, p. 590-5, Dec 1999. ISSN 0945-6317. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10628801 >. KUWAHARA, K. et al. The effects of the selective ROCK inhibitor, Y27632, on ET-1- induced hypertrophic response in neonatal rat cardiac myocytes--possible involvement of Rho/ROCK pathway in cardiac muscle cell hypertrophy. FEBS Lett, v. 452, n. 3, p. 314-8, Jun 1999. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10386613 >. KÜHN, S.; GEYER, M. Formins as effector proteins of Rho GTPases. Small GTPases, v. 5, p. e29513, 2014. ISSN 2154-1256. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24914801 >. KÜMPER, S. et al. Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis. Elife, v. 5, p. e12994, Jan 2016. ISSN 2050- 084X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26765561 >. LAI, S. Y. et al. Activated Vav2 modulates cellular invasion through Rac1 and Cdc42 in oral squamous cell carcinoma. Oral Oncol, v. 44, n. 7, p. 683-8, Jul 2008. ISSN 1368- 8375. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/17996485 >. LEETHANAKUL, C. et al. Distinct pattern of expression of differentiation and growthrelated genes in squamous cell carcinomas of the head and neck revealed by the use of laser capture microdissection and cDNA arrays. Oncogene, v. 19, n. 28, p. 3220-4, Jun 2000. ISSN 0950-9232. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10918578 >. LI, M. et al. Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of huntington disease. PLoS One, v. 8, n. 2, p. e56026, 2013. ISSN 1932-6203. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/23409115 >. LIAO, Y. C. et al. Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene, v. 31, n. 25, p. 3086-97, Jun 2012. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22002306 >. LIU, S. et al. Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res, v. 69, n. 22, p. 8742-51, Nov 2009. ISSN 1538- 7445. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19887617 >. LIU, S. Y. et al. Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma. J Oral Maxillofac Surg, v. 62, n. 6, p. 702-7, Jun 2004. ISSN 0278-2391. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15170282 >. LÓPEZ, R. V. et al. Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection. Cancer Causes Control, v. 25, n. 4, p. 461-71, Apr 2014. ISSN 1573-7225. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/24474236 >. MA, Z. et al. p66(Shc) restrains Ras hyperactivation and suppresses metastatic behavior. Oncogene, v. 29, n. 41, p. 5559-67, Oct 2010. ISSN 1476-5594. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20676142 >. MADDALA, R. et al. Growth factor induced activation of Rho and Rac GTPases and actin cytoskeletal reorganization in human lens epithelial cells. Mol Vis, v. 9, p. 329-36, Jul 2003. ISSN 1090-0535. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12876554 >. MALUMBRES, M.; BARBACID, M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer, v. 9, n. 3, p. 153-66, Mar 2009. ISSN 1474-1768. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19238148 >. MALUMBRES, M. et al. CDK inhibitors in cancer therapy: what is next? Trends Pharmacol Sci, v. 29, n. 1, p. 16-21, Jan 2008. ISSN 0165-6147. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/18054800 >. MAMMOTO, A. et al. Role of RhoA, mDia, and ROCK in cell shape-dependent control of the Skp2-p27kip1 pathway and the G1/S transition. J Biol Chem, v. 279, n. 25, p. 26323-30, Jun 2004. ISSN 0021-9258. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15096506 >. MASSAGUÉ, J. G1 cell-cycle control and cancer. Nature, v. 432, n. 7015, p. 298-306, Nov 2004. ISSN 1476-4687. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15549091 >. MASSANO, J. et al. Oral squamous cell carcinoma: review of prognostic and predictive factors. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, v. 102, n. 1, p. 67-76, Jul 2006. ISSN 1528-395X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16831675 >. MATSUMURA, F. Regulation of myosin II during cytokinesis in higher eukaryotes. Trends Cell Biol, v. 15, n. 7, p. 371-7, Jul 2005. ISSN 0962-8924. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15935670 >. MAZIERES, J. et al. Loss of RhoB expression in human lung cancer progression. Clin Cancer Res, v. 10, n. 8, p. 2742-50, Apr 2004. ISSN 1078-0432. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/15102679 >. MERAJVER, S. D.; USMANI, S. Z. Multifaceted role of Rho proteins in angiogenesis. J Mammary Gland Biol Neoplasia, v. 10, n. 4, p. 291-8, Oct 2005. ISSN 1083-3021. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/16900393 >. MERTSCH, S.; THANOS, S. Opposing signaling of ROCK1 and ROCK2 determines the switching of substrate specificity and the mode of migration of glioblastoma cells. Mol Neurobiol, v. 49, n. 2, p. 900-15, Apr 2014. ISSN 1559-1182. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24170433 >. METTOUCHI, A. et al. Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Mol Cell, v. 8, n. 1, p. 115-27, Jul 2001. ISSN 1097- 2765. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11511365 >. MIKURIYA, Y. et al. Fatty liver creates a pro-metastatic microenvironment for hepatocellular carcinoma through activation of hepatic stellate cells. Int J Cancer, v. 136, n. 4, p. E3-13, Feb 2015. ISSN 1097-0215. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25053237 >. MINETA, H. et al. Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma. Cancer, v. 85, n. 5, p. 1011-7, Mar 1999. ISSN 0008-543X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10091782 >. MISHRA, A. K.; LAMBRIGHT, D. G. Invited review: Small GTPases and their GAPs. Biopolymers, v. 105, n. 8, p. 431-48, Aug 2016. ISSN 1097-0282. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26972107 >. MONTALVO, J. et al. ROCK1 & 2 perform overlapping and unique roles in angiogenesis and angiosarcoma tumor progression. Curr Mol Med, v. 13, n. 1, p. 205-19, Jan 2013. ISSN 1875-5666. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22934846 >. MONTORO, J. R. et al. Prognostic factors in squamous cell carcinoma of the oral cavity. Braz J Otorhinolaryngol, v. 74, n. 6, p. 861-6, 2008 Nov-Dec 2008. ISSN 1808-8694. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/19582342 >. MOREIRA CARBONI, S. E. S. et al. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, v. 26, n. 9, p. 923-30, Oct 2015. ISSN 1473-5741. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26181228 >. MOREIRA CARBONI, S. S. et al. HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma. Anticancer Drugs, Jul 2015. ISSN 1473-5741. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26181228 >. MORGAN-FISHER, M.; WEWER, U. M.; YONEDA, A. Regulation of ROCK activity in cancer. J Histochem Cytochem, v. 61, n. 3, p. 185-98, Mar 2013. ISSN 1551-5044. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23204112 >. NANCI, A. Ten Cate's Oral Histology Development, Structure and Function 8 a edição. Montreal: 2013. 398. NIGGLI, V. Rho-kinase in human neutrophils: a role in signalling for myosin light chain phosphorylation and cell migration. FEBS Lett, v. 445, n. 1, p. 69-72, Feb 1999. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10069376 >. NILIUS, B. et al. Role of Rho and Rho kinase in the activation of volume-regulated anion channels in bovine endothelial cells. J Physiol, v. 516 ( Pt 1), p. 67-74, Apr 1999. ISSN 0022-3751. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10066923 >. NOBES, C.; MARSH, M. Dendritic cells: new roles for Cdc42 and Rac in antigen uptake? Curr Biol, v. 10, n. 20, p. R739-41, Oct 2000. ISSN 0960-9822. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11069097 >. OHASHI, K. et al. Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem, v. 275, n. 5, p. 3577-82, Feb 2000. ISSN 0021-9258. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10652353 >. OLSON, M. F. Applications for ROCK kinase inhibition. Curr Opin Cell Biol, v. 20, n. 2, p. 242-8, Apr 2008. ISSN 0955-0674. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/18282695 >. PAN, P. et al. Advances in the development of Rho-associated protein kinase (ROCK) inhibitors. Drug Discov Today, v. 18, n. 23-24, p. 1323-33, Dec 2013. ISSN 1878-5832. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/24076262 >. PENG, J. et al. ROCK cooperated with ET-1 to induce epithelial to mesenchymal transition through SLUG in human ovarian cancer cells. Biosci Biotechnol Biochem, v. 76, n. 1, p. 42-7, 2012. ISSN 1347-6947. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/22232246 >. PERNIS, A. B. et al. Rho Kinases in Autoimmune Diseases. Annu Rev Med, v. 67, p. 355- 74, 2016. ISSN 1545-326X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26768244 >. PINHEIRO, N. M. Papel Funcional das GTPases Rho na proliferação e Diferenciação Celular em Carcinoma Epidermóide Oral. 2010. 109 Universidade Federal do Triângulo Mineiro POLLARD, T., D.; EARNSHAW, W. C. Biologia Celular. 2006. PRENDERGAST, G. C. Actin' up: RhoB in cancer and apoptosis. Nat Rev Cancer, v. 1, n. 2, p. 162-8, Nov 2001. ISSN 1474-175X. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11905808 >. PULTE, D.; BRENNER, H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist, v. 15, n. 9, p. 994-1001, 2010. ISSN 1549-490X. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/20798198 >. RAISOVA, M. et al. Resistance to CD95/Fas-induced and ceramide-mediated apoptosis of human melanoma cells is caused by a defective mitochondrial cytochrome c release. FEBS Lett, v. 473, n. 1, p. 27-32, May 2000. ISSN 0014-5793. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10802053 >. REYMOND, N. et al. RhoC and ROCKs regulate cancer cell interactions with endothelial cells. Mol Oncol, v. 9, n. 6, p. 1043-55, Jun 2015. ISSN 1878-0261. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25677806 >. RIDLEY, A. J. Rho GTPase signalling in cell migration. Curr Opin Cell Biol, v. 36, p. 103- 112, Sep 2015. ISSN 1879-0410. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/26363959 >. ROCHELLE, T. et al. p210bcr-abl induces amoeboid motility by recruiting ADF/destrin through RhoA/ROCK1. FASEB J, v. 27, n. 1, p. 123-34, Jan 2013. ISSN 1530-6860. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23047898 >. SAHAI, E. et al. Transformation mediated by RhoA requires activity of ROCK kinases. Curr Biol, v. 9, n. 3, p. 136-45, Feb 1999. ISSN 0960-9822. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10021386 >. SAMUEL, M. S. et al. Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth. Cancer Cell, v. 19, n. 6, p. 776-91, Jun 2011. ISSN 1878-3686. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/21665151 >. SASAKI, Y.; SUZUKI, M.; HIDAKA, H. The novel and specific Rho-kinase inhibitor (S)-(+)- 2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine as a probing molecule for Rho-kinase-involved pathway. Pharmacol Ther, v. 93, n. 2-3, p. 225-32, 2002 FebMar 2002. ISSN 0163-7258. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/12191614 >. SAUTER, E. R. et al. Cyclin D1 is a candidate oncogene in cutaneous melanoma. Cancer Res, v. 62, n. 11, p. 3200-6, Jun 2002. ISSN 0008-5472. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/12036934 >. SAWADA, N.; LIAO, J. K. Rho/Rho-associated coiled-coil forming kinase pathway as therapeutic targets for statins in atherosclerosis. Antioxid Redox Signal, v. 20, n. 8, p. 1251-67, Mar 2014. ISSN 1557-7716. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23919640 >. SCHMITZ, A. A. et al. Rho GTPases: signaling, migration, and invasion. Exp Cell Res, v. 261, n. 1, p. 1-12, Nov 2000. ISSN 0014-4827. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11082269 >. SCHNELZER, A. et al. Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. Oncogene, v. 19, n. 26, p. 3013-20, Jun 2000. ISSN 0950-9232. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/10871853 >. SCHOFIELD, A. V.; BERNARD, O. Rho-associated coiled-coil kinase (ROCK) signaling and disease. Crit Rev Biochem Mol Biol, v. 48, n. 4, p. 301-16, 2013 Jul-Aug 2013. ISSN 1549-7798. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23601011 >. SCIUBBA, J. J. Oral cancer and its detection. History-taking and the diagnostic phase of management. J Am Dent Assoc, v. 132 Suppl, p. 12S-18S, Nov 2001. ISSN 0002-8177. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11803647 >. SCULLY, C.; BAGAN, J. Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. Oral Dis, v. 15, n. 6, p. 388-99, Sep 2009. ISSN 1601-0825. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/19371401 >. SEASHOLTZ, T. M. et al. Rho and Rho kinase mediate thrombin-stimulated vascular smooth muscle cell DNA synthesis and migration. Circ Res, v. 84, n. 10, p. 1186-93, May 1999. ISSN 0009-7330. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/10347093 >. SEBBAGH, M. et al. Direct cleavage of ROCK II by granzyme B induces target cell membrane blebbing in a caspase-independent manner. J Exp Med, v. 201, n. 3, p. 465- 71, Feb 2005. ISSN 0022-1007. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/15699075 >. SHI, J. et al. Dissecting the roles of ROCK isoforms in stress-induced cell detachment. Cell Cycle, v. 12, n. 10, p. 1492-500, May 2013. ISSN 1551-4005. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23598717 >. SHI, J.; WEI, L. Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil. J Cardiovasc Pharmacol, v. 62, n. 4, p. 341-54, Oct 2013. ISSN 1533- 4023. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/23921309 >. SQUIER, C. A.; KREMER, M. J. Biology of oral mucosa and esophagus. J Natl Cancer Inst Monogr, n. 29, p. 7-15, 2001. ISSN 1052-6773. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/11694559 >. SUN, K. et al. Curcumin inhibits LPA-induced invasion by attenuating RhoA/ROCK/MMPs pathway in MCF7 breast cancer cells. Clin Exp Med, v. 16, n. 1, p. 37-47, Feb 2016. ISSN 1591-9528. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/25596714 >. TAKAI, Y.; SASAKI, T.; MATOZAKI, T. Small GTP-binding proteins. Physiol Rev, v. 81, n. 1, p. 153-208, Jan 2001. ISSN 0031-9333. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/11152757 >. TAKEBA, Y. et al. The Rho kinase inhibitor fasudil is involved in p53-mediated apoptosis in human hepatocellular carcinoma cells. Cancer Chemother Pharmacol, v. 69, n. 6, p. 1545-55, Jun 2012. ISSN 1432-0843. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/22481618 >. TSELIOU, M. et al. The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells. Cell Physiol Biochem, v. 38, n. 1, p. 94-109, 2016. ISSN 1421-9778. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/26741994 >. UEHATA, M. et al. Calcium sensitization of smooth muscle mediated by a Rhoassociated protein kinase in hypertension. Nature, v. 389, n. 6654, p. 990-4, Oct 1997. ISSN 0028-0836. Disponível em: < https://www.ncbi.nlm.nih.gov/pubmed/9353125 >. VAN AELST, L.; D'SOUZA-SCHOREY, C. Rho GTPases and signaling networks. Genes Dev, v. 11, n. 18, p. 2295-322, Sep 1997. ISSN 0890-9369. Disponível em: < http://www.ncbi.nlm.nih.gov/pubmed/9308960 >. VARGAS-FERREIRA, F. et al. Etiologic factors associated with oral sq
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFTM
instname:Universidade Federal do Triangulo Mineiro (UFTM)
instacron:UFTM
instname_str Universidade Federal do Triangulo Mineiro (UFTM)
instacron_str UFTM
institution UFTM
reponame_str Biblioteca Digital de Teses e Dissertações da UFTM
collection Biblioteca Digital de Teses e Dissertações da UFTM
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)
repository.mail.fl_str_mv bdtd@uftm.edu.br||bdtd@uftm.edu.br
_version_ 1797221126468796416