OGT Controls the Expression and the Glycosylation of E‐cadherin, and Affects Glycosphingolipid Structures in Human Colon Cell Lines

Colorectal cancer (CRC) affects both women and men living in societies with a high sedentary lifestyle. Amongstthe phenotypic changes exhibited by tumor cells, a widerange of glycosylationshas been reported for colon cancer-derived cell lines and CRC tissues. These aberrant modifications affect different aspectsof glycosylation, including an increase in core fucosylation and GlcNAc branching on N-glycans, alteration of O-glycans, upregulated sialylation and O-GlcNAcylation. Although O-GlcNAcylation and complex glycosylations differ in many aspects, sparse evidences report on the interference of O-GlcNAcylation with complex glycosylation. Nevertheless, this relationship is still a matter of debate. Combining different approaches onthree human colon cell lines (HT29, HCT116 and CCD841CoN), we herein report that silencing O-GlcNAc transferase (OGT, the sole enzyme driving O-GlcNAcylation), only slightly affectsoverall N-and O-glycosylation patterns. Interestingly, silencingof OGT in HT29 cells upregulates E-cadherin (a major actor of epithelial-to-mesenchymal transition) and changes its glycosylation.On the other hand, OGT silencing perturbs biosynthesis ofglycosphingolipids resulting ina decreaseingangliosidesandan increase in globosides.Together, these results provide novel insights regarding the selective regulation of complex glycosylations by O-GlcNAcylation in colon cancer cells. 19;21-22