The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulates the tyrosine phosphorylation of β-catenin

The enzyme GnT-III (beta1,4-N-acetylglucosaminyltransferase III) catalyzes the addition of a bisecting N-acetylglucosamine (GlcNAc) residue on glycoproteins. Our previous study described that the transfection of GnT-lll into mouse melanoma cells results in the enhanced expression of E-cadherin, which in turn leads to, the suppression of lung metastasis. It has recently been proposed that the phosphorylation of a tyrosine residue of beta -catenin is associated with cell migration. The present study reports on the importance of bisecting GlcNAc residues by GnT-III on tyrosine phosphorylation of beta -catenin using three types of cancer cell lines. An addition of bisecting GlcNAc residues to E-cadherin leads to an alteration in cell morphology and the localization of beta -catenin after epidermal growth factor stimulation. These changes are the result of a down-regulation in the tyrosine phosphorylation of beta -catenin, In addition, tyrosine phosphorylation of beta -catenin by transfection of constitutively active c-src was suppressed in GnT-III transfectants as well as in the case of epidermal growth factor stimulation. Treatment with tunicamycin abolished any differences in beta -catenin phosphorylation for the mock vis a vis the GnT-III transfectants. Thus, the addition of a specific N-glycan structure, the bisecting GlcNAc to E-cadherin-beta -catenin complex, down-regulates the intracellular signaling pathway, suggesting its implication in cell motility and the suppression of cancer metastasis.