Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/58189 |
Resumo: | 2030 |
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Reis, Jhenifer Santos dosSantos, Marcos Andre Rodrigues da CostaCosta, Kelli Monteiro daLIma, Celio Geraldo Freire deMorrot, AlexandrePreviato, Jose OsvaldoPreviato, Lucia MendonçaFonseca, Leonardo Marques daLima, Leonardo Friere de2023-05-06T17:53:09Z2023-05-06T17:53:09Z2023REIS, Jhenifer Santos dos Reis et al. Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells. Matrix Biology, v. 118, p. 47-68, 2023.0945-053Xhttps://www.arca.fiocruz.br/handle/icict/5818910.1016/,matblo.2023.03.002engElsevier B.V,Maior expressão do forma patológica O-glicosiladaFibronectina oncofetalFenótipo de resistênciaMúltiplas drogas de células cancerosasIn the multidrug resistanceIncreased expression of the pathological O-glycosylated formOncofetal fibronectinPhenotype of cancer cellsMultidrug resistanceIncreased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2030Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ , Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil.Changes in protein glycosylation are a hallmark of transformed cells and modulate numerous phenomena associated with cancer progression, such as the acquisition of multidrug resistance (MDR) phenotype. Different families of glycosyltransferases and their products have already been described as possible modulators of the MDR phenotype. Among the glycosyltransferases intensively studied in cancer research, UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 (pp-GalNAc-T6), which is widely expressed in many organs and tissues, stands out. Its influence in several events associated with kidney, oral, pancreatic, renal, lung, gastric and breast cancer progression has already been described. However, its participation in the MDR phenotype has never been studied. Here, we demonstrate that human breast adenocarcinoma MCF-7 MDR cell lines, generated by chronic exposure to doxorubicin, in addition to exhibiting increased expression of proteins belonging to the ABC superfamily (ABCC1 and ABCG2), and anti-apoptotic proteins (Blcl-2 and Bcl-xL), also present high expression of pp-GalNAc-T6, the enzyme currently proposed as the main responsible for the biosynthesis of oncofetal fibronectin (onf-FN), a major extracellular matrix component expressed by cancer cells and embryonic tissues, but absent in healthy cells. Our results show that onf-FN, which is generated by the addition of a GalNAc unit at a specific threonine residue inside the type III homology connective segment (IIICS) domain of FN, is strongly upregulated during the acquisition of the MDR phenotype. Also, the silencing of pp-GalNAc-T6, not only compromises the expression of the oncofetal glycoprotein, but also made the MDR cells more sensitive to all anticancer drugs tested, partially reversing the MDR phenotype. Taken together, our results demonstrate for the first time the upregulation of the Oglycosylated oncofetal fibronectin, as well as the direct participation of pp-GalNAc-T6 during the acquisition of a MDR phenotype in a breast cancer model, giving credence to the hypothesis that in transformed cells, glycosyltransferases and/or their products, such as unusual extracellular matrix glycoproteins can be used as potential therapeutic targets for the treatment of cancer.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/58189/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALJenniferSantos_AlexandeMorrot_etal_IOC_2023.pdfJenniferSantos_AlexandeMorrot_etal_IOC_2023.pdfapplication/pdf3368889https://www.arca.fiocruz.br/bitstream/icict/58189/2/JenniferSantos_AlexandeMorrot_etal_IOC_2023.pdf8d3092a952402de0204541cf9925e739MD52icict/581892023-09-14 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dc.title.en_US.fl_str_mv |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
title |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
spellingShingle |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells Reis, Jhenifer Santos dos Maior expressão do forma patológica O-glicosilada Fibronectina oncofetal Fenótipo de resistência Múltiplas drogas de células cancerosas In the multidrug resistance Increased expression of the pathological O-glycosylated form Oncofetal fibronectin Phenotype of cancer cells Multidrug resistance |
title_short |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
title_full |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
title_fullStr |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
title_full_unstemmed |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
title_sort |
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells |
author |
Reis, Jhenifer Santos dos |
author_facet |
Reis, Jhenifer Santos dos Santos, Marcos Andre Rodrigues da Costa Costa, Kelli Monteiro da LIma, Celio Geraldo Freire de Morrot, Alexandre Previato, Jose Osvaldo Previato, Lucia Mendonça Fonseca, Leonardo Marques da Lima, Leonardo Friere de |
author_role |
author |
author2 |
Santos, Marcos Andre Rodrigues da Costa Costa, Kelli Monteiro da LIma, Celio Geraldo Freire de Morrot, Alexandre Previato, Jose Osvaldo Previato, Lucia Mendonça Fonseca, Leonardo Marques da Lima, Leonardo Friere de |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Reis, Jhenifer Santos dos Santos, Marcos Andre Rodrigues da Costa Costa, Kelli Monteiro da LIma, Celio Geraldo Freire de Morrot, Alexandre Previato, Jose Osvaldo Previato, Lucia Mendonça Fonseca, Leonardo Marques da Lima, Leonardo Friere de |
dc.subject.other.en_US.fl_str_mv |
Maior expressão do forma patológica O-glicosilada Fibronectina oncofetal Fenótipo de resistência Múltiplas drogas de células cancerosas In the multidrug resistance |
topic |
Maior expressão do forma patológica O-glicosilada Fibronectina oncofetal Fenótipo de resistência Múltiplas drogas de células cancerosas In the multidrug resistance Increased expression of the pathological O-glycosylated form Oncofetal fibronectin Phenotype of cancer cells Multidrug resistance |
dc.subject.en.en_US.fl_str_mv |
Increased expression of the pathological O-glycosylated form Oncofetal fibronectin Phenotype of cancer cells Multidrug resistance |
description |
2030 |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-05-06T17:53:09Z |
dc.date.available.fl_str_mv |
2023-05-06T17:53:09Z |
dc.date.issued.fl_str_mv |
2023 |
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.citation.fl_str_mv |
REIS, Jhenifer Santos dos Reis et al. Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells. Matrix Biology, v. 118, p. 47-68, 2023. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/58189 |
dc.identifier.issn.en_US.fl_str_mv |
0945-053X |
dc.identifier.doi.none.fl_str_mv |
10.1016/,matblo.2023.03.002 |
identifier_str_mv |
REIS, Jhenifer Santos dos Reis et al. Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells. Matrix Biology, v. 118, p. 47-68, 2023. 0945-053X 10.1016/,matblo.2023.03.002 |
url |
https://www.arca.fiocruz.br/handle/icict/58189 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.publisher.none.fl_str_mv |
Elsevier B.V, |
publisher.none.fl_str_mv |
Elsevier B.V, |
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reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
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Repositório Institucional da FIOCRUZ (ARCA) |
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