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.
Hiscox
S
S
Department of Surgery, University of Wales College of Medicine, Health Park, Cardiff, U.K. Hiscox@cf.ac.uk
Jiang
W G
WG
D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D018613:Microscopy, Confocal; D010766:Phosphorylation; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D017228:Hepatocyte Growth Factor