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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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.
Total Authors: 10
Document type: Journal article
Source: ONCOTARGET; v. 7, n. 50, p. 83570-83587, DEC 13 2016.
Web of Science Citations: 7
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. (AU)

FAPESP's process: 12/06875-6 - Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology
Grantee:Emerson Soares Bernardes
Support Opportunities: Research Grants - Young Investigators Grants