Epithelial-Mesenchymal Transition in Development and Cancer
Jean Paul Thiery, Ph.D.
Epithelial-Mesenchymal Transition (EMT) is a fundamental mechanism governing morphogenesis that employs multiple signaling pathways to shape the embryo. The intriguing possibility that similar mechanisms operate in carcinomas has been documented repeatedly in experimental models, with the discovery of mesenchymal phenotypes in tumor subsets. The transition from an epithelial carcinoma to a mesenchymal-like state is potentially associated with increased stemness, therapeutic resistance, and immune escape. In this presentation we shall review mechanisms driving EMT during gastrulation and the formation of the neural crest. We shall present recent data on adhesive mechanisms involved in the maintenance of an epithelial state versus the transition to a mesenchymal-like phenotype. We then will discuss studies supporting the concept that EMT contributes to tumor progression. In ovarian serous adenocarcinoma, we show that two out of five molecular subtypes exhibit a strongly transitioned or ‘EMTed’ phenotype. These mesenchymal-like cell lines exhibit enhanced invasive properties and clonogenicity, as compared with epithelial-like cell lines, and are associated with a significantly worse prognosis. Interestingly, however, we show that ovarian carcinoma lines display a spectrum of EMT phenotypes, including intermediary states. Our current strategy is aimed at designing new therapeutic approaches that interfere with the plasticity of ovarian carcinoma cells using drug combinations, with the ultimate hope to improve the response of carcinoma cells to conventional cytotoxics by reversing EMT and rescuing an epithelial phenotype.
Jean Paul Thiery1,2,3, Raymond Lee1,James Weston6, VirgileViasnoff4, Wilfried Engl4, Sylvie Dufour5, Wen Jing Sim1, Kelvin Chua3, Seiichi Mori3 andRuby Huang3
Institute of Molecular Cell Biology1, A*STAR, Department of Biochemistry2, Cancer Science Institute3, Mechanobiology Institute4, National University of Singapore, Republic of Singapore, Institut Curie Paris France5, University of Eugene, Oregon USA6