Definition of a direct extracellular interaction between Met and E-cadherin.
High levels of the Met tyrosine kinase receptor expression are associated with metastatic disease. Met activation by hepatocyte growth factor (HGF) is associated with decreased E-cadherin-dependent cell-cell contacts. The molecular mechanism underlying this process remains unclear. To better understand the relationship between E-cadherin and Met, we assessed Met localization in cells which form mature E-cadherin-dependent adhesion HT-29 and cells which have lost E-cadherin expression BT-549. Met colocalized with E-cadherin at the site of cell-cell adhesion in HT-29 cells, but Met was distributed in an intracellular compartment in BT-549 cells. Forced expression of E-cadherin in BT-549 cells recruited Met to the membrane. Cross-linking studies suggested that Met and E-cadherin interact in the extracellular domain in HT-29 cells. This is the first evidence of a physical interaction between Met and E-cadherin. We suggest that this receptor/cadherin pairing may be a mechanism for cellular presentation of receptors in a manner that localizes them optimally for interaction with ligand.
Reshetnikova
Galina
G
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA. greshet@mail.cytspb.rssi.ru
Troyanovsky
Sergei
S
Rimm
David L
DL
D001943:Breast Neoplasms / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D003432:Cross-Linking Reagents; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013347:Subcellular Fractions; D014407:Tumor Cells, Cultured
D015820:Cadherins; D003432:Cross-Linking Reagents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met