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https://observatorio.fm.usp.br/handle/OPI/18793
Title: | O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer |
Authors: | SANTOS, Sofia N.; JUNQUEIRA, Mara S.; FRANCISCO, Guilherme; VILANOVA, Manuel; MAGALHAES, Ana; BARUFFI, Marcelo Dias; CHAMMAS, Roger; HARRIS, Adrian L.; REIS, Celso A.; BERNARDES, Emerson S. |
Citation: | ONCOTARGET, v.7, n.50, p.83570-83587, 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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MDR Artigos e Materiais de Revistas Científicas - HC/ICESP Artigos e Materiais de Revistas Científicas - LIM/24 Artigos e Materiais de Revistas Científicas - ODS/03 |
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