No one-way street: cross-talk between e-cadherin and receptor tyrosine kinase (RTK) signaling: a mechanism to regulate RTK activity

Cancer Biol Ther. 2005 Jan;4(1):28-31. doi: 10.4161/cbt.4.1.1431. Epub 2005 Jan 15.


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 b-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 extracellular 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.

Publication types

  • Review

MeSH terms

  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cadherins / physiology*
  • Cell Adhesion
  • Cell Movement
  • Down-Regulation
  • ErbB Receptors / physiology*
  • Humans
  • Neoplasms / physiopathology*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction


  • Cadherins
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases