Article Dans Une Revue Proteomics Année : 2019

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

James Biwi
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Résumé

Colorectal cancer (CRC) affects both women and men living in societies with a high sedentary lifestyle. Amongst the phenotypic changes exhibited by tumor cells, a wide range of glycosylations has been reported for colon cancer-derived cell lines and CRC tissues. These aberrant modifications affect different aspects of 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 on three 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 affects overall N- and O-glycosylation patterns. Interestingly, silencing of 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 of glycosphingolipids resulting in a decrease in gangliosides and an increase in globosides. Together, these results provide novel insights regarding the selective regulation of complex glycosylations by O-GlcNAcylation in colon cancer cells.

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hal-02319622 , version 1 (11-10-2024)

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James Biwi, Charlotte Clarisse, Christophe Biot, Radoslaw Pawel Kozak, Katarina Madunic, et al.. OGT Controls the Expression and the Glycosylation of E‐cadherin, and Affects Glycosphingolipid Structures in Human Colon Cell Lines. Proteomics, 2019, 19 (21-22), pp.1800452. ⟨10.1002/pmic.201800452⟩. ⟨hal-02319622⟩

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