| Summary: | Chad J Creighton,1–3 Don L Gibbons,4,5 Jonathan M Kurie4 1The Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA; 2Department of Medicine, Baylor College of Medicine, Houston, TX, USA; 3Department of Bioinformatics and Computational Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Thoracic/Head and Neck Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Epithelial–mesenchymal transition (EMT) is involved in normal developmental cellular processes, but it may also be co-opted by a subset of cancer cells, to enable them to invade and form metastases at distant sites. Several gene transcription factors regulate EMT, including Snail1, Snail2, Zeb1, Zeb2, and Twist; ongoing studies continue to identify and elucidate other drivers. Specific micro ribonucleic acids (RNAs) have also been found to regulate EMT, including the microRNA-200 (miR-200) family, which targets Zeb1/Zeb2. Cancer “stem cells” – with the ability to self-renew and to regenerate all the cell types within the tumor – have been found to express EMT markers, further implicating both cancer stem cells and EMT with metastasis. Microenvironmental cues, including transforming growth factor-β, can direct EMT tumor metastasis, such as by regulating miR-200 expression. In human tumors, EMT markers and regulators may be expressed in a subset of tumor cells, such as in cells at the invasive front or tumor–microenvironment interface, though certain subtypes of cancer can show widespread mesenchymal-like features. In terms of therapeutic targeting of EMT in patients, potential areas of exploration could include targeting the cancer stem cell subpopulation, as well as microRNA-based therapeutics that reintroduce miR-200. This review will examine evidence for a role of EMT in invasion and metastasis, with the focus being on studies in lung and breast cancers. We also carry out analyses of publicly-available gene expression profiling datasets in order to show how EMT-associated genes appear coordinately expressed across human tumor specimens. Keywords: EMT, epithelial–mesenchymal transition, tumor microenvironment, miR-200, cancer stem cells
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