Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways

Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts-an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner beta-catenin to be necessary, but not sufficient, for induction of these phenotypes. In…

• WM
  W. M. Keck Foundation
• MI
  Massachusetts Institute of Technology
• BI
  Broad Institute
• DF
  Directorate for Biological Sciences
• LC
  Ludwig Center at Harvard