BACKGROUND: E-cadherin is a cell-cell adhesion molecule and the dysfunction of 
which is a common feature of more than 70% of all invasive carcinomas, including 
gastric cancer. Mechanisms behind the loss of E-cadherin function in gastric 
carcinomas include mutations and silencing at either the DNA or RNA level. 
Nevertheless, in a high percentage of gastric carcinoma cases displaying 
E-cadherin dysfunction, the mechanism responsible for E-cadherin dysregulation 
is unknown. We have previously demonstrated the existence of a bi-directional 
cross-talk between E-cadherin and two major N-glycan processing enzymes, 
N-acetylglucosaminyltransferase-III or -V (GnT-III or GnT-V).
METHODS: In the present study, we have characterized the functional implications 
of the N-glycans catalyzed by GnT-III and GnT-V on the regulation of E-cadherin 
biological functions and in the molecular assembly and stability of 
adherens-junctions in a gastric cancer model. The results were validated in 
human gastric carcinoma samples.
RESULTS: We demonstrated that GnT-III induced a stabilizing effect on E-cadherin 
at the cell membrane by inducing a delay in the turnover rate of the protein, 
contributing for the formation of stable and functional adherens-junctions, and 
further preventing clathrin-dependent E-cadherin endocytosis. Conversely, GnT-V 
promotes the destabilization of E-cadherin, leading to its mislocalization and 
unstable adherens-junctions with impairment of cell-cell adhesion.
CONCLUSIONS: This supports the role of GnT-III on E-cadherin-mediated tumor 
suppression, and GnT-V on E-cadherin-mediated tumor invasion.
GENERAL SIGNIFICANCE: These results contribute to fill the gap of knowledge of 
those human carcinoma cases harboring E-cadherin dysfunction, opening new 
insights into the molecular mechanisms underlying E-cadherin regulation in 
gastric cancer with potential translational clinical applications.