Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/119047
Author(s): Santos, S
Junqueira, M
Francisco, G
Vilanova, M
Magalhães, A
Baruffi, M
Chammas, R
Harris, A
Reis, CA
Bernardes, E
Title: O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer
Publisher: Impact Journals
Issue Date: 2016
Abstract: ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I.
Subject: Animals
Antigens, Tumor-Associated, Carbohydrate/genetics
Antigens, Tumor-Associated, Carbohydrate/metabolism
Antineoplastic Agents/pharmacology
Cell Line, Tumor
Cell Proliferation
Cisplatin/pharmacology
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Galectin 3/metabolism
Glycosylation
Humans
Mice, Inbred BALB C
Mice, Nude
Protein Processing, Post-Translational
Protein Transport
RNA Interference
Sialyltransferases/genetics
Sialyltransferases/metabolism
Stomach Neoplasms/drug therapy
Stomach Neoplasms/genetics
Stomach Neoplasms/metabolism
Stomach Neoplasms/pathology
Time Factors
Transfection
Tumor Burden
URI: https://hdl.handle.net/10216/119047
Source: Oncotarget, vol.7(50), p. 83570-83587
Related Information: info:eu-repo/grantAgreement/FCT/COMPETE/132983/PT
info:eu-repo/grantAgreement/FCT/COMPETE/125428/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/licenses/by/3.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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