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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Genome‐wide identification of miR‐200 targets reveals a regulatory network controlling cell invasion
Cameron P. Bracken,Cameron P. Bracken,Xiaochun Li,Josephine A. Wright,David M. Lawrence,Katherine A. Pillman,Marika Salmanidis,Matthew A Anderson,B. Kate Dredge,Philip A. Gregory,Philip A. Gregory,Anna Tsykin,Corine T. Neilsen,Daniel Thomson,Andrew G. Bert,Joanne M. Leerberg,Alpha S. Yap,Kirk B. Jensen,Yeesim Khew-Goodall,Yeesim Khew-Goodall,Gregory J. Goodall,Gregory J. Goodall +21 more
TL;DR: Functional characterization of the miR‐200 targets indicates that they constitute subnetworks that underlie the ability of cancer cells to migrate and invade, including coordinate effects on Rho‐ROCK signaling, invadopodia formation, MMP activity, and focal adhesions.
Journal ArticleDOI
Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds
TL;DR: This review focuses on transcriptional regulation, non-coding RNAs, alternative splicing events and cell adhesion molecules regulation during EMT and summarizes the knowledge with regard to the small potentially druggable molecules capable of modulating EMT for cancer therapy.
Journal ArticleDOI
MicroRNA-200 Family Members Differentially Regulate Morphological Plasticity and Mode of Melanoma Cell Invasion
TL;DR: Overall the findings call into question the general role of miR-200 in suppressing invasion and metastasis, and highlight novel distinguishing characteristics of individual mi R-200 family members.
Journal ArticleDOI
miR-141 Is a Key Regulator of Renal Cell Carcinoma Proliferation and Metastasis by Controlling EphA2 Expression
Xuanyu Chen,Xuegang Wang,Anming Ruan,Weiwei Han,Yan Zhao,Xing Lu,Pei Xiao,Hangchuan Shi,Rong Wang,Li Chen,Shaoyong Chen,Quansheng Du,Hongmei Yang,Xiaoping Zhang +13 more
TL;DR: In this paper, microarray-based miRNA profiling of clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-141 both in vitro and in vivo, which was significantly downregulated in ccRCC tissues.
Journal ArticleDOI
MicroRNAs: critical regulators of epithelial to mesenchymal (EMT) and mesenchymal to epithelial transition (MET) in cancer progression
TL;DR: The understanding of EMT has been significantly improved by the characterization of miRNAs that influence the signalling pathways and downstream events that define EMT on a molecular level.
References
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