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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TLDR
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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MiR-429 increases the metastatic capability of HCC via regulating classic Wnt pathway rather than epithelial-mesenchymal transition.
Jing Tang,Liang Li,Wentao Huang,Chengjun Sui,Yang Yingcheng,Xi-Meng Lin,Guojun Hou,Xin Chen,Jing Fu,Sheng-xian Yuan,Shao Li,Wen Wen,Shanhua Tang,Dan Cao,Meng-Chao Wu,Lei Chen,Hongyang Wang,Hongyang Wang +17 more
TL;DR: In this article, the authors identified the hypomethylated status and upregulation of miR-429 in portal vein metastasis samples in comparison with their matched primary tumor.
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Epigenetic Regulation of Inflammatory Cytokine-Induced Epithelial-To-Mesenchymal Cell Transition and Cancer Stem Cell Generation
TL;DR: The molecular regulatory feedback loops and networks involved in inflammatory cytokine-induced EMT and CSC generation, including DNA and histone modifying enzymes and micoRNAs are reviewed.
Journal ArticleDOI
Fbxw7 regulates tumor apoptosis, growth arrest and the epithelial-to-mesenchymal transition in part through the RhoA signaling pathway in gastric cancer.
TL;DR: The results suggest that Fbxw7 induces apoptosis and growth arrest and inhibits the EMT in part by down-regulating the RhoA signaling pathway.
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Molecular Regulation of Parturition: A Myometrial Perspective
Nora E. Renthal,Koriand'r C. Williams,Alina P. Montalbano,Chien Cheng Chen,Lu Gao,Carole R. Mendelson +5 more
TL;DR: The molecular mechanisms that mediate myometrial quiescence and contractility and their regulation by the two central hormones of pregnancy, P4 and estradiol-17β are focused on and the integrative roles of microRNAs also are considered.
Journal Article
USP51 promotes deubiquitination and stabilization of ZEB1
Zhicheng Zhou,Peijing Zhang,Xiaoyu Hu,Jongchan Kim,Fan Yao,Zhenna Xiao,Zhenna Xiao,Liyong Zeng,Liang Chang,Yutong Sun,Li Ma +10 more
TL;DR: It is suggested that USP51 is a ZEB1 deubiquitinase that may serve as an alternative pathway for targeting the cancer-promoting transcriptional factor Z EB1.
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).