Epithelial-mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation

In this review, we explore the connections between epithelial-mesenchymal transition (EMT) and differentiation status. EMTs in development have been described as differentiation events, while in most cases EMTs in cancer have been depicted as dedifferentiation events. We will briefly summarize both embryo development and cancer progression with regard to the involvement of EMT and cell differentiation status. We further present the studies that provide evidence that EMT results in both differentiation and dedifferentiation. Finally, we present our resolution to this dilemma by suggesting that EMT brings about dedifferentiation that enables subsequent differentiation. In normal development, EMT events may cause a partial reversal of differentiation to overcome differentiation barriers. When EMT is aberrantly activated in cancer, cells gain attributes of stem cells that contribute to self-renewal capabilities and are able to differentiate to all cell types represented in the tumor. The resulting cancer stem cells attain hallmarks of cancer, including replicative immortality, resistance to cell death, and invasiveness. Developmental Dynamics 248:10-20, 2019. © 2018 Wiley Periodicals, Inc.