Modulation of N-glycosylation by mesalamine facilitates membranous E-cadherin expression in colon epithelial cells

Biochem Pharmacol. 2014 Jan 15;87(2):312-20. doi: 10.1016/j.bcp.2013.10.021. Epub 2013 Oct 30.


Genome wide association studies have implicated intestinal barrier function genes in the pathogenesis of ulcerative colitis. One of such loci CDH1, encoding E-cadherin, a transmembrane glycoprotein with known tumor suppressor functions, is also linked to the susceptibility to colorectal cancer. Loss of membranous E-cadherin expression is common in both colitis and cancer. We have recently demonstrated that mesalamine (5-ASA); the anti-inflammatory drug used to treat ulcerative colitis, induces membranous expression of E-cadherin and increases intercellular adhesion. Using colorectal cancer epithelial cells with aberrant E-cadherin expression, we investigated the mechanism underlying such an effect of 5-ASA. Post-translational modification of E-cadherin glycosylation was analyzed by biotin/streptavidin detection of sialylated glycoproteins. GnT-III (N-acetylglucosaminyltransferase III) expression was assessed by qRT-PCR, Western blot and immunofluorescence. GnT-III activity was analyzed by reactivity with E-4/L-4-PHA. Expression, localization and interaction of E-cadherin and β-catenin were analyzed by Western blot, immunocytochemistry and RNA interference. 5-ASA activity modulated E-cadherin glycosylation and increased both mRNA and protein levels of GnT-III and its activity as detected by increased E4-lectin reactivity. Intestinal APC(Min) polyps in mice showed low expression of GnT-III and 5-ASA was effective in increasing its expression. The data demonstrated that remodeling of glycans by GnT-III mediated bisect glycosylation, contributes to the membranous retention of E-cadherin by 5-ASA; facilitating intercellular adhesion. Induction of membranous expression of E-cadherin by 5-ASA is a novel mechanism for mucosal healing in colitis that might impede tumor progression by modulation of GnT-III expression.

Keywords: 5-ASA; AJ; CRC; E-cadherin; Glycosylation; GnT-III; IBD; N-acetylglucosaminyltransferase-III; PAK1; UC; Ulcerative colitis; adherens junction; colorectal cancer; inflammatory bowel diseases; p21 activated kinase 1; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cadherins / biosynthesis*
  • Colon / drug effects
  • Colon / metabolism*
  • Colon / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glycosylation / drug effects
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / pathology
  • Male
  • Mesalamine / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cadherins
  • Mesalamine