title: 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 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.
authors.affiliation: Gastroenterology Division, Department of Medicine, Abramson Cancer Center and Family Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Claudia D
authors.initials: CD
authors.lastname: Andl
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
mesh_terms: D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement; D015536:Down-Regulation; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D015820:Cadherins; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases