The ZEB/miR-200 feedback loop--a motor of cellular plasticity in development and cancer?
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.
Brabletz
Simone
S
Department of Visceral Surgery, University of Freiburg, Hugstetterstrasse 55, 79106 Freiburg, Germany. thomas.brabletz@uniklinik-freiburg.de
Brabletz
Thomas
T
D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000503:physiopathology*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1