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

Abstract

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 glycosylation 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), it is herein reported 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.

Roles of ten‑eleven translocation family proteins and their O‑linked β‑N‑acetylglucosaminylated forms in cancer development (Review)

“…OGT activity is associated with epithelial-mesenchymal transition (EMT), p53, Wnt and TGF-β signaling pathways, inflammatory responses and apoptosis in cervical cancer cells ( 44 ). Knockdown of OGT in colon cells results in upregulation and altered glycosylation of E-cadherin, an important factor in EMT progression and may disrupt biosynthesis of glycosphingolipids (lactosylceramide, gangliosides and globosides), with consequent reduction of gangliosides (ganglioside 3 and ganglioside 2) but increase of globosides (globoside 3 and globoside 4) ( 45 ). Chronic lymphocytic leukemia (CLL) cells demonstrate high expression of O-GlcNAcylated proteins, including p53, c-Myc, and Akt and enhanced protein glycosylation alters intracellular signaling processes (p53 and PI3K/AKT/mTOR signaling pathways) in these cells ( 46 ).…”

Insights into the Role of Sialylation in Cancer Metastasis, Immunity, and Therapeutic Opportunity

“…O-GlcNAc can be identified through galactosylation and then sialylation [ 99 , 100 ]. O-GlcNAcylation regulates the sialylation of glycosphingolipids and impacts cell-cell interactions as well as signal transduction in human non-pathogenic or cancerous colon cells [ 101 ]. How specific sialylation levels and glycoforms trigger signal transduction to switch on/off cancer spread remains a mystery.…”

Association between Inflammation and Function of Cell Adhesion Molecules Influence on Gastrointestinal Cancer Development

“…O-GlcNAc transferase (OGT) catalyzes the process of O-GlcNAcylation. Silencing of OGT reduces O-GlcNAcylation levels and increases N-glycosylation of E-cadherin, which leads to enhanced cell junctions and suppression of migration in colorectal cancer [143]. Core 1 β1,3-galactosyltransferase (C1GALT1), overexpressed in HCC, promotes invasive ability through modifying O-glycosylation of integrin β1 [144].…”