Epithelial to Mesenchymal Transition

The epithelial to mesenchymal transition (EMT) is a complex phenotypic event that drives cells to forego their extensive epithelial cell-cell contacts, apical basal polarity and distinct cytoskeletal architecture to become more motile and invasive. These attributes of mesenchymal cells, along with the propensity to develop stemness characteristics and chemoresistance, make EMT a dangerous program to establish during cancer progression. Transforming growth factor β (TGFβ) is one prominent extracellular initiator of EMT. In this review, we discuss the mechanisms of TGFβ signaling, and subsequently the resulting developmental and pathological manifestations. Furthermore, extensive research has examined the role of EMT in metastasis mediated by TGFβ and other elements. This review highlights the hypotheses that exist to understand EMTs function in metastasis largely through the examination of animal model experiments. EMT targeted therapies have been used in clinical trials to varying degrees of success. It is important to understand the vast literature in preclinical animal model experiments to improve the efficacy of EMT targeted trials in the clinic. The mechanisms of action for current EMT targeted therapies, and additional insights into mechanisms that may be targeted in the future, are discussed with a primary focus on those inhibiting TGFβ signaling.