Association of the HGF/SF receptor, c-met, with the cell-surface adhesion molecule, E-cadherin, and catenins in human tumor cells

Tumour cell metastatic potential is significantly enhanced following treatment with HGF/SF, the ligand for the c-met receptor tyrosine kinase, Following c-met activation in tumour cells, phosphorylation of beta-catenin occurs, together with loss of intercellular adhesion and a gain in the motile and invasive nature of the cell. In this study we show that c-met is colocalised with beta-catenin and E-cadherin at regions of cell-cell contact in human colon cancer (HRT18 and HT115) and two breast cancer (MCF7 and MDA MB 231) cell lines. Immunoprecipitation studies demonstrated an association between c-met and members of the cadherin adhesion complex in these epithelial tumour cells, along with the membrane tyrosine protein phophatase, PTP mu. We conclude that the HGF/SF receptor, c-met, together with members of the cadherin/ catenin cell-cell adhesion system and PTP mu, may form part of a protein complex in E-cadherin positive tumour cells that acts to regulate intercellular adhesion following HGF/SF stimulation, (C) 1999 Academic Press.