No one-way street: Cross-talk between E-cadherin and receptor tyrosine kinase (RTK) signaling: A mechanism to regulate RTK activity

Abstract

E-cadherin was originally viewed exclusively as a structural protein mediating cell-cell adhesion. More recently, its signaling functions have been recognized. Loss or downregulation of E-cadherin releases proteins, such as β-catenin and p120 catenin, from a membrane-bound state into the cytoplasm, which are known to regulate transcriptional activity. E-cadherin is known to interact with receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR). However, previously, only the regulation of E-cadherin mediated adhesion through EGFR has been described and activation of EGFR was implicated in loss of cell adhesion, and increased cell migration and invasion. Now, Qian et al. (EMBO J 2004, 23:1739-48) describe that E-cadherin mediated adhesion inhibits receptor tyrosine kinase (RTK) activity. E-cadherin was found to interact through its extra-cellular domain with EGFR and other receptor tyrosine kinases, thereby decreasing receptor mobility and ligand-affinity. This is a novel mechanism by which E-cadherin inhibits RTKs, and suggests that downregulation of E-cadherin may contribute to the frequently observed activation of RTKs in tumors. ©2005 Landes Bioscience.