Soluble E-cadherin promotes cell survival by activating epidermal growth factor receptor

Exp Cell Res. 2011 Apr 1;317(6):838-48. doi: 10.1016/j.yexcr.2010.12.025. Epub 2011 Jan 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cadherins / metabolism
  • Cadherins / pharmacology*
  • Cell Survival / drug effects
  • ErbB Receptors / metabolism*
  • Gene Expression Regulation / drug effects*
  • HEK293 Cells
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction / drug effects
  • Solubility


  • Cadherins
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Oncogene Protein v-akt
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3