O-mannosylation and N-glycosylation: two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer

Oncotarget. 2016 Oct 4;7(40):65231-65246. doi: 10.18632/oncotarget.11245.


Dysregulation of tumor suppressor protein E-cadherin is an early molecular event in cancer. O-mannosylation profile of E-cadherin is a newly-described post-translational modification crucial for its adhesive functions in homeostasis. However, the role of O-mannosyl glycans in E-cadherin-mediated cell adhesion in cancer and their interplay with N-glycans remains largely unknown. We herein demonstrated that human gastric carcinomas exhibiting a non-functional E-cadherin display a reduced expression of O-mannosyl glycans concomitantly with increased modification with branched complex N-glycans. Accordingly, overexpression of MGAT5-mediated branched N-glycans both in gastric cancer cells and transgenic mice models led to a significant decrease of O-mannosyl glycans attached to E-cadherin that was associated with impairment of its tumour suppressive functions. Importantly, overexpression of protein O-mannosyltransferase 2 (POMT2) induced a reduced expression of branched N-glycans which led to a protective effect of E-cadherin biological functions. Overall, our results reveal a newly identified mechanism of (dys)regulation of E-cadherin that occur through the interplay between O-mannosylation and N-glycosylation pathway.

Keywords: E-cadherin; N-glycosylation; O-mannosylation; gastric cancer.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Cadherins / metabolism*
  • Glycosylation
  • Humans
  • Mannose / metabolism
  • Mice
  • Mice, Transgenic
  • Polysaccharides
  • Protein Processing, Post-Translational / physiology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Suppressor Proteins / metabolism*


  • Cadherins
  • Polysaccharides
  • Tumor Suppressor Proteins
  • Mannose