دورية أكاديمية
Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells.
| العنوان: | Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells. |
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| المؤلفون: | Reis JSD; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., Santos MARDC; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., da Costa KM; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., Freire-de-Lima CG; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., Morrot A; Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Rio de Janeiro, RJ 21941-902, Brazil; Fiocruz, Instituto Oswaldo Cruz, Laboratório de Imunoparasitologia, Rio de Janeiro, RJ 21040-360, Brazil., Previato JO; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., Previato LM; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., da Fonseca LM; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil., Freire-de-Lima L; Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Laboratório de Biologia Celular de Glicoconjugados, Rio de Janeiro, RJ 21941-902, Brazil. Electronic address: leolima@biof.ufrj.br. |
| المصدر: | Matrix biology : journal of the International Society for Matrix Biology [Matrix Biol] 2023 Apr; Vol. 118, pp. 47-68. Date of Electronic Publication: 2023 Mar 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9432592 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1569-1802 (Electronic) Linking ISSN: 0945053X NLM ISO Abbreviation: Matrix Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Stuttgart ; New York : Fischer, c1994- |
| مواضيع طبية MeSH: | Breast Neoplasms*/drug therapy , Breast Neoplasms*/genetics, Humans ; Female ; Glycosylation ; Glycosyltransferases ; Drug Resistance, Multiple/genetics |
| مستخلص: | 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 O-glycosylated 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. Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Extracellular matrix components; Glycoproteins; Glycosyltransferases; Multidrug resistance phenotype; O-glycosylation; Oncofetal fibronectin; pp-GalNAc-T3; pp-GalNAc-T6 |
| المشرفين على المادة: | 0 (oncofetal fibronectin) EC 2.4.- (Glycosyltransferases) |
| تواريخ الأحداث: | Date Created: 20230307 Date Completed: 20230331 Latest Revision: 20230413 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.matbio.2023.03.002 |
| PMID: | 36882122 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1569-1802 |
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| DOI: | 10.1016/j.matbio.2023.03.002 |