| Author | Reis, Jhenifer Santos dos | |
| Author | Santos, Marcos Andre Rodrigues da Costa | |
| Author | Costa, Kelli Monteiro da | |
| Author | LIma, Celio Geraldo Freire de | |
| Author | Morrot, Alexandre | |
| Author | Previato, Jose Osvaldo | |
| Author | Previato, Lucia Mendonça | |
| Author | Fonseca, Leonardo Marques da | |
| Author | Lima, Leonardo Friere de | |
| Access date | 2023-05-06T17:53:09Z | |
| Available date | 2023-05-06T17:53:09Z | |
| Document date | 2023 | |
| Citation | 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. | en_US |
| ISSN | 0945-053X | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/58189 | |
| Language | eng | en_US |
| Publisher | Elsevier B.V, | en_US |
| Rights | open access | |
| Subject in Portuguese | Maior expressão do forma patológica O-glicosilada | en_US |
| Subject in Portuguese | Fibronectina oncofetal | en_US |
| Subject in Portuguese | Fenótipo de resistência | en_US |
| Subject in Portuguese | Múltiplas drogas de células cancerosas | en_US |
| Subject in Portuguese | In the multidrug resistance | en_US |
| Title | Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells | en_US |
| Type | Article | |
| DOI | 10.1016/,matblo.2023.03.002 | |
| Abstract | 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. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho., Laboratorio de Biologia Celular de Glicoconjugados. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | Increased expression of the pathological O-glycosylated form | en_US |
| Subject | Oncofetal fibronectin | en_US |
| Subject | Phenotype of cancer cells | en_US |
| Subject | Multidrug resistance | en_US |
| Embargo date | 2030 | |
