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.

TrendsThe epithelial–mesenchymal transition (EMT) program is a naturally occurring transdifferentiation program that governs changes of cell states along the epithelial versus mesenchymal axis and confers epithelial–mesenchymal plasticity upon epithelial cells.Activation of the EMT program places normal and neoplastic epithelial cells in states where they are poised to enter into stem cell compartments.During development and cancer pathogenesis, the EMT program is induced by several synergistic contextual signals.Epithelial–mesenchymal plasticity is critical for carcinoma progression and metastasis. Inhibition of EMT activation and/or epithelial–mesenchymal plasticity may serve as new ways to clinically treat advanced carcinomas.