Target cell movement in tumor and cardiovascular diseases based on the epithelial–mesenchymal transition concept ☆ Kian-Ngiap Chua, Kar Lai Poon, Jormay Lim, Wen-Jing Sim, Ruby Yun-Ju Huang, Jean Paul Thiery ⁎ Institute of Molecular Cell Biology, Experimental Therapeutic Centre, Biopolis A*STAR, Cancer Science Institute National University of Singapore and Department of Obstetrics and Gynaecology, National University Hospital, Singapore, Republic of Singapore abstract article info Article history: Received 9 December 2010 Accepted 9 February 2011 Available online 16 February 2011 Keywords: Epithelial–mesenchymal transition Carcinoma Invasion Metastasis Heart Fibrosis Coronary disease Regeneration Epithelial–mesenchymal transition (EMT) is a fundamental mechanism in development driving body plan formation. EMT describes a transition process wherein polarized epithelial cells lose their characteristics and acquire a mesenchymal phenotype. The apico-basal polarity of epithelial cells is replaced by a front-rear polarity in mesenchymal cells which favor cell–extracellular matrix than intercellular adhesion. These events serve as a prerequisite to the context-dependent migratory and invasive functions of mesenchymal cells. In solid tumors, carcinoma cells undergoing EMT not only invade and metastasize but also exhibit cancer stem cell-like properties, providing resistance to conventional and targeted therapies. In cardiovascular systems, epicardial cells engaged in EMT contribute to myocardial regeneration. Conversely, cardiovascular endothelial cells undergoing EMT cause cardiac fibrosis. Growing evidence has shed light on the potential development of novel therapeutics that target cell movement by applying the EMT concept, and this may provide new therapeutic strategies for the treatment of cancer and heart diseases. © 2011 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 558 2. Carcinoma invasion and metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 2.1. Attributes of the EMT program during carcinoma progression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 2.2. EMT and tumor microenvironment of metastasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 2.3. Cancer prognosis and EMT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560 2.4. Therapeutics against EMT drivers in carcinoma progression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561 2.5. Anti-EMT therapeutics as potential agents to reverse acquired resistance during treatment . . . . . . . . . . . . . . . . . . . . . . 561 3. EMT in heart ontogeny and diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 3.1. EMT–MET cycles in heart morphogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562 3.1.1. EndMT in endocardial cushion formation of the heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 3.1.2. Epicardial EMT in the coronary vasculature formation of the heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563 3.2. The role of EndMT in cardiac fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 3.3. The role of epicardial EMT in zebrafish heart regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 564 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565 1. Introduction Epithelial–mesenchymal transition (EMT) is a fundamental pro- cess driving morphogenesis in most metazoans conserved throughout evolution. Cells engaged in the EMT program will undergo complex changes in cell architecture and behavior. In a typical epithelial layer, epithelial cells develop intercellular junctions and adhesive structures between adjacent cells such as tight junctions, adherens junctions, Advanced Drug Delivery Reviews 63 (2011) 558–567 ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Target Cell Movement in Tumor and Cardiovascular Diseases”. ⁎ Corresponding author. E-mail address: jpthiery@imcb.a-star.edu.sg (J.P. Thiery). 0169-409X/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2011.02.003 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr