O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer

Journal article

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.

Authors: Santos, S; Junqueira, M; Francisco, G; Vilanova, M; Magalhães, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Impact Journals
• Journal: Oncotarget
• Volume: 7
• Issue: 50
• Pages: 83570-53587
• Publication date: 2016-11-08
• Acceptance date: 2016-10-21
• DOI: 10.18632/oncotarget.13192
• ISSN: 1949-2553
• Language: English
• Keywords: glycosylation; galectin-3; gastric cancer; chemotherapy resistance; sialyl-Tn