Oral Presentation 14th International Biennial Conference on Metastasis Research 2012

EMT in the progression of carcinoma (#6)

Jean Paul Thiery 1 2 3 , Virgile Viasnoff 4 , Wilfried Engl 4 , Sylvie Dufour 5 , Wen Jing Sim 2 , Kelvin Chua 3 , Seiichi Mori 3 , Ruby Huang 3
  1. National University, Singapore
  2. Institute of Molecular and Cell Biology, Proteos, Republic of Singapore
  3. Department of Biochemistry, Cancer Science Institute, A*STAR, Singapore, Republic of Singapore
  4. National University of Singapore, Mechanobiology Institute, Singapore , Republic of Singapore
  5. Institut Curie Paris, Paris, France

Epithelial-Mesenchymal Transition (EMT) is a fundamental mechanism governing morphogenesis, employing multiple signaling pathways to shape the embryo. The intriguing possibility that similar mechanisms operate in carcinomas has been documented repeatedly in experimental models, characterizing 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. We shall first present recent data on the adhesive mechanisms involved in the maintenance of the epithelial state or conferring mesenchymal-like phenotypes. We shall then discuss studies supporting the concept that EMT contributes to tumor progression. In ovarian serous adenocarcinoma, two out of five molecular subtypes exhibit a strong EMT phenotype associated with a significantly worse prognosis. We have also identified an EMT spectrum in ovarian carcinoma lines. Mesenchymal-like cell lines exhibit enhanced invasive properties and clonogenicity as compared with epithelial-like cell lines.  Our current strategy is aimed at designing new therapeutic approaches that interfere with the plasticity of ovarian carcinoma cells using a combination of drugs, with the ultimate hope that the reversal to a more epithelial phenotype will improve patient response to conventional cytotoxics.