Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells

Detalhes bibliográficos
Autor(a) principal: Reis, Jhenifer Santos dos
Data de Publicação: 2023
Outros Autores: 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
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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spelling 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; 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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
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier B.V,
publisher.none.fl_str_mv Elsevier B.V,
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/58189/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/58189/2/JenniferSantos_AlexandeMorrot_etal_IOC_2023.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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