Hepatocyte growth factor/scatter factor disrupts epithelial tumour cell-cell adhesion: involvement of beta-catenin.

Initial events in the metastatic spread of tumours involve loss of cell-cell adhesion within the primary tumour mass. The integrity and morphology of epithelial tumour cell colonies is maintained primarily by cell-cell adhesions mediated by E-cadherin and its associated intracellular catenin molecules. Hepatocyte growth factor/scatter factor (HGF/SF) is a potent promoter of the metastatic functions of tumour cells, including motility and invasion and also induces the dissociation of tumour cell colonies. In this study we report that HGF/SF promoted the scattering of an epithelial colorectal tumour cell line. Western blotting demonstrated that this was not due to a change in level of either E-cadherin or its associated catenin molecules. Immunoprecipitation studies revealed that HGF/SF elevated the level of tyrosine-phosphorylated beta-catenin within these cells together with reducing the amount of E-cadherin that was observed to co-precipitate with the beta-catenin. These results were confirmed with confocal scanning laser microscopy. We conclude that phosphorylation of beta-catenin by HGF/SF affects its association with E-cadherin at the cell surface and thus regulates E-cadherin function resulting in colony scattering phenomena.