Protein O-GlcNAcylation Regulates beta-catenin, E-cadherin and Cell Motility

The Wnt/ β-catenin signaling pathway and cadherin-mediated adhesion are implicated in epithelial-mesenchymal transition (EMT), a
key cellular process in invasion and metastasis. Often, deregulation
of the Wnt pathway is caused by altered phosphorylation of its components. Specifically, phosphorylation of Ser or Thr residues of
β-catenin affects its location and interaction with E-cadherin, thus
facilitates cell-cell adhesion. O-GlcNAcylation, the addition of
O-GlcNAc to Ser or Thr, is comparable with phosphorylation and
may compete with it on the same or adjacent residues. Consistently
with previous studies, the current study indicates that β-catenin and
E-cadherin are O-GlcNAcylated. To test the effect of
O-GlcNAcylation on cell motility and how O-GlcNAcylation might
affect β-catenin and E-cadherin functions, O-GlcNAcase, the
enzyme responsible for the removal of O-GlcNAc, was inhibited.
This inhibition resulted in a global elevation of protein
O-GlcNAcylation, increased expression of E-cadherin and
β-catenin, and altered β-catenin translocation in fibroblasts.
Concomitantly with O-GlcNAcylation elevation, fibroblast cell motility was enhanced. The effect of O-GlcNAcylation on β-catenin
transcriptional activity is now under investigation. The results
described herein may support the notion that O-GlcNAcylation
affects EMT and cell motility through the regulation of β-catenin
and E-cadherin, which may further influence metastasis and wound
healing.