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

EMBO Reports - Tập 11 Số 9 - Trang 670-677 - 2010
Simone Brabletz1, Thomas Brabletz2,1
1Department of Visceral Surgery, University of Freiburg Hugstetterstrasse 55 79106 Freiburg Germany
2Comprehensive Cancer Center Freiburg, University of Freiburg Hugstetterstrasse 55 79106 Freiburg Germany

Tóm tắt

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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