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://repositorio-aberto.up.pt/handle/10216/90888
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:ICBAS - Artigo em Revista Científica Internacional

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