| Full text | |
| 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 |