An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530)

R. Y J Huang, M. K. Wong, T. Z. Tan, K. T. Kuay, A. H. C Ng, V. Y. Chung, Y. S. Chu, N. Matsumura, H. C. Lai, Y. F. Lee, W. J. Sim, C. Chai, E. Pietschmann, S. Mori, J. J H Low, M. Choolani, J. P. Thiery

研究成果: 雜誌貢獻文章

192 引文 斯高帕斯(Scopus)

摘要

The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise. Different degrees of epithelial-mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others. Numerous studies have focused on bona fide epithelial and mesenchymal states but rarely on intermediate states. In this study, we describe a model system for appraising the spectrum of EMT using 43 well-characterised OC cell lines. Phenotypic EMT characterisation reveals four subgroups: Epithelial, Intermediate E, Intermediate M and Mesenchymal, which represent different epithelial-mesenchymal compositions along the EMT spectrum. In cell-based EMT-related functional studies, OC cells harbouring an Intermediate M phenotype are characterised by high N-cadherin and ZEB1 expression and low E-cadherin and ERBB3/HER3 expression and are more anoikis-resistant and spheroidogenic. A specific Src-kinase inhibitor, Saracatinib (AZD0530), restores E-cadherin expression in Intermediate M cells in in vitro and in vivo models and abrogates spheroidogenesis. We show how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS). We conclude that the characterisation of intermediate EMT states provides a new approach to better define EMT. The concept of the EMT Spectrum allows the utilisation of EMT genes as predictive markers and the design and application of therapeutic targets for reversing EMT in a selective subgroup of patients.

原文英語
文章編號e915
期刊Cell Death and Disease
4
發行號11
DOIs
出版狀態已發佈 - 十一月 2013
對外發佈Yes

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

指紋 深入研究「An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530)」主題。共同形成了獨特的指紋。

  • 引用此

    Huang, R. Y. J., Wong, M. K., Tan, T. Z., Kuay, K. T., C Ng, A. H., Chung, V. Y., Chu, Y. S., Matsumura, N., Lai, H. C., Lee, Y. F., Sim, W. J., Chai, C., Pietschmann, E., Mori, S., Low, J. J. H., Choolani, M., & Thiery, J. P. (2013). An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530). Cell Death and Disease, 4(11), [e915]. https://doi.org/10.1038/cddis.2013.442