title: Soluble E-cadherin promotes cell survival by activating epidermal growth factor receptor.
abstract: High levels of the soluble form of E-cadherin can be found in the serum of cancer patients and are associated with poor prognosis. Despite the possible predictive value of soluble E-cadherin, little is understood concerning its patho-physiological consequences in tumor progression. In this study, we show that soluble E-cadherin facilitates cell survival via functional interaction with cellular E-cadherin. Exposure of cells to a recombinant form of soluble E-cadherin, at a concentration found in cancer patient's serum, prevents apoptosis due to serum/growth factor withdrawal, and inhibits epithelial lumen formation, a process that requires apoptosis. Further, soluble E-cadherin-mediated cell survival involves activation of the epidermal growth factor receptor (EGFR) and EGFR-mediated activation of both phosphoinositide-3 kinase (PI3K)/AKT and ERK1/2 signaling pathways. These results are evidence of a complex functional interplay between EGFR and E-cadherin and also suggest that the presence of soluble E-cadherin in cancer patients' sera might have relevance to cell survival and tumor progression.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Landon J
authors.initials: LJ
authors.lastname: Inge
authors.forename: Sonali P
authors.initials: SP
authors.lastname: Barwe
authors.forename: Julia
authors.initials: J
authors.lastname: D'Ambrosio
authors.forename: Jegan
authors.initials: J
authors.lastname: Gopal
authors.forename: Kan
authors.initials: K
authors.lastname: Lu
authors.forename: Sergey
authors.initials: S
authors.lastname: Ryazantsev
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Rajasekaran
authors.forename: Ayyappan K
authors.initials: AK
authors.lastname: Rajasekaran
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility
chemical_list: D015820:Cadherins; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3