Please use this identifier to cite or link to this item:
https://hdl.handle.net/10216/90888
Author(s): | Sofia mN. Santos Mara S. Junqueira Guilherme Francisco Manuel Vilanova Ana Magalhães Marcelo Dias Baruffi Roger Chammas Adrian L. Harris Celso Reis Emerson S. Bernardes |
Title: | O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer |
Issue Date: | 2016-11-08 |
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: | Medicina, Ciências médicas e da saúde Medicine, Medical and Health sciences |
Scientific areas: | Ciências médicas e da saúde Medical and Health sciences |
URI: | https://hdl.handle.net/10216/90888 |
Document Type: | Artigo em Revista Científica Internacional |
Rights: | openAccess |
Appears in Collections: | ICBAS - Artigo em Revista Científica Internacional |
Files in This Item:
File | Description | Size | Format | |
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175601.pdf | 8.02 MB | Adobe PDF | View/Open |
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