RNAI-based strategies to to target ST6GalNAc-I in vivo and improve chemotherapy sensitivity in gastric cancer

ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. We have recently shown that: 1) 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; 2) exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected; 3) the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors and; 4) 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 and open perspectives for the development of siRNA delivery nanoparticles to target galectin-3 and/or ST6GalNAc-I in vivo.