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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Micro-RNAs and breast cancer.
John Le Quesne,Carlos Caldas +1 more
TL;DR: What is known of miR biology in the normal breast, and of their emerging roles in breast cancer are discussed.
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p53-induced miR-15a/16-1 and AP4 form a double-negative feedback loop to regulate epithelial-mesenchymal transition and metastasis in colorectal cancer
TL;DR: A double-negative feedback loop involving miR-15a/16-1 and AP4 that stabilizes epithelial and mesenchymal states, respectively, which may determine metastatic prowess is reported.
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The TGFβ-miR200-Mig6 pathway orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors
Eugene Izumchenko,Xiaofei Chang,Christina Michailidi,Luciane T. Kagohara,Rajani Ravi,Keren Paz,Mariana Brait,Mohammad O. Hoque,Shizhang Ling,Atul Bedi,David Sidransky +10 more
TL;DR: The data demonstrate that the TGFβ-miR200-MIG6 network orchestrates the EMT-associated kinase switch that induces resistance to EGFR inhibitors, and identify a low ratio of MIG6 to miR200 as a promising predictive biomarker of the response of tumors to EG FR TKIs.
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The network of epithelial–mesenchymal transition: potential new targets for tumor resistance
TL;DR: This review highlights the potential key therapeutic targets of EMT linked with tumor aggressiveness, hypoxia, angiogenesis and cancer stem cells, emphasizing on an emerging EMT-associated NF-κB/HER2/STAT3 pathway in radioresistance of breast cancer stem Cells.
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MicroRNAs in colorectal cancer metastasis.
TL;DR: The role of miRNAs in the metastatic pathway of CRC, including escape of apoptosis, epithelial–mesenchymal transition (EMT), angiogenesis, and invasion is reviewed.
References
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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
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