Epithelial–Mesenchymal Plasticity: A Central Regulator of Cancer Progression

The epithelial-mesenchymal transition (EMT) program has emerged as a central driver of tumor malignancy. Moreover, the recently uncovered link between passage through an EMT and acquisition of stem-like properties indicates that activation of the EMT programs serves as a major mechanism for generating cancer stem cells (CSCs); that is, a subpopulation of cancer cells that are responsible for initiating and propagating the disease. In this review, we summarize the evidence supporting the widespread involvement of the EMT program in tumor pathogenesis and attempt to rationalize the connection between the EMT program and acquisition of stem cell traits. We propose that epithelial-mesenchymal plasticity is likely controlled by multiple varients of the core EMT program, and foresee the need to resolve the various programs and the molecular mechanisms that underlie them.Breast Cancer Research FoundationSamuel Waxman Cancer Research FoundationMassachusetts Institute of Technology. Ludwig Center for Cancer ResearchNational Cancer Institute (U.S.).(Program P01-CA080111)National Cancer Institute (U.S.).(Program R01-CA078461)National Cancer Institute (U.S.).(Program U01-CA184897