Definition of a direct extracellular interaction between Met and E-cadherin

Cell Biol Int. 2007 Apr;31(4):366-73. doi: 10.1016/j.cellbi.2007.01.022. Epub 2007 Jan 21.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cadherins / metabolism*
  • Cell Adhesion*
  • Cell Membrane / metabolism*
  • Colonic Neoplasms / metabolism*
  • Cross-Linking Reagents
  • Fluorescent Antibody Technique
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Proto-Oncogene Proteins c-met / metabolism*
  • Subcellular Fractions
  • Tumor Cells, Cultured

Substances

  • Cadherins
  • Cross-Linking Reagents
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met