RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/5458 |
Resumo: | Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas. |
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RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cellsApoptosisCell Line, TumorCell ProliferationCyclin D1G1 Phase Cell Cycle CheckpointsHumansNF-KappaB Inhibitor alphaNF-kappa BSignal TransductionStaurosporineThyroid Epithelial CellsTransfectionrac1 GTP-Binding ProteinGene Expression Regulation, NeoplasticVias de Transdução de Sinal e Patologias AssociadasOverexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas.Public Library of ScienceRepositório Científico do Instituto Nacional de SaúdeFaria, MárciaMatos, PauloPereira, TeresaCabrera, RafaelCardoso, Bruno A.Bugalho, Maria JoãoSilva, Ana Luísa2018-03-22T19:09:09Z2017-02-242017-02-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/5458engPLoS One. 2017 Feb 24;12(2):e0172689. doi: 10.1371/journal.pone.0172689. eCollection 2017.1932-6203)10.1371/journal.pone.0172689info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:40:52Zoai:repositorio.insa.pt:10400.18/5458Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:08.944876Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
title |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
spellingShingle |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells Faria, Márcia Apoptosis Cell Line, Tumor Cell Proliferation Cyclin D1 G1 Phase Cell Cycle Checkpoints Humans NF-KappaB Inhibitor alpha NF-kappa B Signal Transduction Staurosporine Thyroid Epithelial Cells Transfection rac1 GTP-Binding Protein Gene Expression Regulation, Neoplastic Vias de Transdução de Sinal e Patologias Associadas |
title_short |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
title_full |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
title_fullStr |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
title_full_unstemmed |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
title_sort |
RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells |
author |
Faria, Márcia |
author_facet |
Faria, Márcia Matos, Paulo Pereira, Teresa Cabrera, Rafael Cardoso, Bruno A. Bugalho, Maria João Silva, Ana Luísa |
author_role |
author |
author2 |
Matos, Paulo Pereira, Teresa Cabrera, Rafael Cardoso, Bruno A. Bugalho, Maria João Silva, Ana Luísa |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Faria, Márcia Matos, Paulo Pereira, Teresa Cabrera, Rafael Cardoso, Bruno A. Bugalho, Maria João Silva, Ana Luísa |
dc.subject.por.fl_str_mv |
Apoptosis Cell Line, Tumor Cell Proliferation Cyclin D1 G1 Phase Cell Cycle Checkpoints Humans NF-KappaB Inhibitor alpha NF-kappa B Signal Transduction Staurosporine Thyroid Epithelial Cells Transfection rac1 GTP-Binding Protein Gene Expression Regulation, Neoplastic Vias de Transdução de Sinal e Patologias Associadas |
topic |
Apoptosis Cell Line, Tumor Cell Proliferation Cyclin D1 G1 Phase Cell Cycle Checkpoints Humans NF-KappaB Inhibitor alpha NF-kappa B Signal Transduction Staurosporine Thyroid Epithelial Cells Transfection rac1 GTP-Binding Protein Gene Expression Regulation, Neoplastic Vias de Transdução de Sinal e Patologias Associadas |
description |
Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02-24 2017-02-24T00:00:00Z 2018-03-22T19:09:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/5458 |
url |
http://hdl.handle.net/10400.18/5458 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS One. 2017 Feb 24;12(2):e0172689. doi: 10.1371/journal.pone.0172689. eCollection 2017. 1932-6203) 10.1371/journal.pone.0172689 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132143232745472 |