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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A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial–mesenchymal transition
Nam Hee Kim,Hyun Sil Kim,Xiao Yan Li,Inhan Lee,Hyung Seok Choi,Shi Eun Kang,So Young Cha,Joo Kyung Ryu,Dojun Yoon,Eric R. Fearon,R. Grant Rowe,Sanghyuk Lee,Christopher G. Maher,Stephen J. Weiss,Jong In Yook +14 more
TL;DR: Expression of the essential EMT inducer Snail1 is inhibited by miR-34 through a p53-dependent regulatory pathway.
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Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells.
TL;DR: In this article, a mechanistic understanding of prostate cancer recurrence and metastasis is proposed, which is closely linked with the biology of prostate stem cells or cancer-initiating cells that is reminiscent of the acquisition of Epithelial to Mesenchymal Transition (EMT) phenotype.
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G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer
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TL;DR: Methylation of histone H3 on lysine 9 (H3K9me2) is critical for promoter DNA methylation of E-cadherin in three TGF-β-induced EMT model cell lines, as well as in CLBC cell Lines, revealing a critical mechanism underlying the epigenetic regulation of EMT.
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Stem cell fate in cancer growth, progression and therapy resistance
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TL;DR: Better understand the molecular networks underlying the cell plasticity conferred by an EMT or a MET and its functional contribution to malignant tumor progression.
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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