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.