Dominant negative inhibition of the association between β-catenin and c-erbB-2 by N-terminally deleted β-catenin suppresses the invasion and metastasis of cancer cells

Aberrant tyrosine phosphorylation of β-catenin inactivates the E-cadherin-mediated cell adhesion and invasion suppressor system in cancer cells. Elucidation of the association between β-catenin and c-erbB-2 protein prompted us to investigate whether interference with this interaction can change the invasive phenotype. In a human gastric cancer cell line, TMK-1, N-terminally deleted β-catenin, which binds to c-erbB-2 but not to cadherin, inhibited the association between endogenous β-catenin and c-erbB-2 protein, and suppressed the tyrosine phosphorylation of β-catenin. Cells expressing truncated β-catenin exhibited markedly reduced invasiveness in vitro and peritoneal metastasis in vivo, and developed an epithelial morphology. These results suggest that tyrosine phosphorylation of β-catenin regulated by c-erbB-2 protein may play an important role in the invasion, metastasis and morphogenesis of cancer cells and that inhibition of the aberrant tyrosine phosphorylation of β-catenin effectively prevents invasion and metastasis of cancer cells.