Clinical & Experimental Metastasis

, Volume 25, Issue 6, pp 621–628 | Cite as

E-cadherin as an indicator of mesenchymal to epithelial reverting transitions during the metastatic seeding of disseminated carcinomas

  • Alan WellsEmail author
  • Clayton Yates
  • Christopher R. Shepard
Research Paper


Cancer metastasis follows a sequential series of events, and many of the critical steps are distinctly similar to EMT-like transformations that occur during normal embryonic development. A current area of focus is the similarities between how cancer cells interact with the ectopic parenchyma after metastatic spread, and secondary developmental MET events that occur in epithelial tissues that have re-assembled within the embryo from mesenchymal cells. Accumulating evidence suggests a critical role for these secondary events, termed mesenchymal-epithelial transitions (MET) in development and mesenchymal-epithelial reverting transitions (MErT) in cancer. In this situation, metastatic seed cancer cells may inertly become part of the ectopic tissue and therefore surmount the metastatic inefficiencies to which most disseminated cancer cells succumb. Just as a critical EMT event is the downregulation or silencing of E-cadherin, we discuss the role of E-cadherin in cancer-associated MErT at distant metastatic sites and speculate on the implications for the fate of micrometastases that undergo a transition to being E-cadherin positive.


Cancer dissemination Differentiation Growth factor receptors Tumor dormancy 



The authors thank the support from the VA Merit Program, the DoD’s Congressionally Directed Medical Research Programs on Prostate and Breast Cancer, and the National Institute of General Medical Sciences.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Alan Wells
    • 1
    Email author
  • Clayton Yates
    • 2
  • Christopher R. Shepard
    • 1
  1. 1.Department of PathologyPittsburgh VA Medical Center and University of PittsburghPittsburghUSA
  2. 2.Department of BiologyTuskegee UniversityTuskegeeUSA

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