A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells
Ulrike Burk,Joerg Schubert,Ulrich F. Wellner,Otto Schmalhofer,Elizabeth Vincan,Simone Spaderna,Thomas Brabletz +6 more
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Results indicate that ZEB1 triggers an microRNA‐mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells, and thus explain the strong intratumorous heterogeneity observed in many human cancers.Abstract:
The embryonic programme 'epithelial-mesenchymal transition' (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc-finger E-box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA-200 family members miR-141 and miR-200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor beta2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA-mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.read more
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Signaling mechanisms of the epithelial-mesenchymal transition
TL;DR: This review discusses how intracellular pathways and extracellular signals that regulate gene expression to induce EMT crosstalk and respond to signals from the microenvironment to regulate the expression and function of EMT-inducing transcription factors in development, physiology, and disease.
Journal ArticleDOI
MicroRNAs in development and disease.
Danish Sayed,Maha Abdellatif +1 more
TL;DR: The discovery, structure, and mode of function of miRNAs in mammalian cells are described, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with the existing knowledge of their targets.
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A Double-Negative Feedback Loop between ZEB1-SIP1 and the microRNA-200 Family Regulates Epithelial-Mesenchymal Transition
Cameron P. Bracken,Philip A. Gregory,Natasha Kolesnikoff,Andrew G. Bert,Jun Wang,M. Frances Shannon,Gregory J. Goodall +6 more
TL;DR: A double-negative feedback loop controlling ZEB1-SIP1 and miR-200 family expression that regulates cellular phenotype is established and has direct relevance to the role of these factors in tumor progression.
Journal ArticleDOI
Epithelial–mesenchymal plasticity in carcinoma metastasis
Jeff H. Tsai,Jing Yang +1 more
TL;DR: The functional requirement of EMT and/or MET during the individual steps of tumor metastasis is reviewed and the potential of targeting this program when treating metastatic diseases is discussed.
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MicroRNA and cancer.
Martin D. Jansson,Anders H. Lund +1 more
TL;DR: The current knowledge and concepts concerning the involvement of microRNAs in cancer, which have emerged from the study of cell culture and animal model systems, including the regulation of key cancer‐related pathways, such as cell cycle control and the DNA damage response are summarized.
References
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Journal Article
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Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).