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

• Type: Article in International Scientific Journal
• Date: 2016-11-08

Authors

Sofia mN. Santos (Author) Other; Mara S. Junqueira (Author) Other; Guilherme Francisco (Author) Other; Manuel Vilanova (Author) ICBAS; Ana Magalhães (Author) Other; Marcelo Dias Baruffi (Author) Other; Roger Chammas (Author) Other; Adrian L. Harris (Author) Other; Celso Reis (Author) ICBAS; Emerson S. Bernardes (Author) Other

Journal

Title: Oncotarget

Vol. 7

Pages: 83570-83587

ISSN: 1949-2553

Publisher: Impact Journals

Indexing

ISI Web of Knowledge - 25 Citations

ISI Web of Science

Scopus - 27 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences

CORDIS: Health sciences > Medical sciences > Medicine

Other information

Authenticus ID: P-00M-DKM

DOI: 10.18632/oncotarget.13192

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18