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 co-localised 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, PTPmu. We conclude that the HGF/SF receptor, c-met, together with members of the cadherin/catenin cell-cell adhesion system and PTPmu, may form part of a protein complex in E-cadherin positive tumour cells that acts to regulate intercellular adhesion following HGF/SF stimulation.
Hiscox
S
S
Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, Wales, CF14 4XN, United Kingdom. Hiscox@cf.ac.uk
Jiang
W G
WG
D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D003110:Colonic Neoplasms / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019859:Proto-Oncogene Proteins c-met; C516862:PTPRN protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8