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EMBO Rep. 2010 Sep;11(9):670-7. doi: 10.1038/embor.2010.117. Epub 2010 Aug 13.

The ZEB/miR-200 feedback loop--a motor of cellular plasticity in development and cancer?

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Department of Visceral Surgery, University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany.


Epithelial-to-mesenchymal transition (EMT) is a fundamental process in development and disease. Zinc-finger enhancer binding (ZEB) transcription factors (ZEB1 and ZEB2) are crucial EMT activators, whereas members of the miR-200 family induce epithelial differentiation. They are reciprocally linked in a feedback loop, each strictly controlling the expression of the other. Now data show that EMT not only confers cellular motility, but also induces stem-cell properties and prevents apoptosis and senescence. Thus the balanced expression of ZEB factors and miR-200 controls all these processes. We therefore propose that the ZEB/miR-200 feedback loop is the molecular motor of cellular plasticity in development and disease, and in particular is a driving force for cancer progression towards metastasis by controlling the state of cancer stem cells.

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