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[Cancer Research 66, 8319-8326, September 1, 2006]
© 2006 American Association for Cancer Research

Reviews

Reassessing Epithelial to Mesenchymal Transition as a Prerequisite for Carcinoma Invasion and Metastasis

Jason J. Christiansen1 and Ayyappan K. Rajasekaran2

1 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, and 2 Molecular Biology Institute and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California

Requests for reprints: Ayyappan K. Rajasekaran, Department of Pathology and Laboratory Medicine, Room 13-344 CHS, University of California, Los Angeles, Los Angeles, CA 90095. Phone: 310-825-1199; Fax: 310-267-2410; E-mail: arajasekaran{at}mednet.ucla.edu.

For most carcinomas, progression toward malignancy is accompanied by loss of epithelial differentiation and a shift towards a mesenchymal phenotype. This process, referred to as epithelial to mesenchymal transition (EMT), exacerbates motility and invasiveness of many cell types and is often considered a prerequisite for tumor infiltration and metastasis. However, there are numerous examples of advanced carcinomas that adopt some mesenchymal features, yet retain characteristics of well-differentiated epithelial cells. We provide a review of these reports and describe mechanisms to explain the morphologic and molecular heterogeneity and plasticity of malignant carcinoma cells, including incomplete EMT, reversion to an epithelial phenotype, and collective migration. We suggest that these mechanisms can manifest in a series of independent and reversible steps and that EMT represents just one mechanism in the global metastatic carcinoma development process. (Cancer Res 2006; 66(17): 8319-26)




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