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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Regulation of EMT by TGFβ in cancer.
TL;DR: Transforming growth factor‐β (TGFβ) suppresses tumor formation since it inhibits cell growth and promotes apoptosis, but in advanced cancers TGFβ elicits tumor promoting effects through its ability to induce epithelial‐mesenchymal transition (EMT) which enhances invasiveness and metastasis.
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TGF-β–induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops
Jingyu Zhang,Jingyu Zhang,Xiao-Jun Tian,Hang Zhang,Yue Teng,Ruoyan Li,Fan Bai,Subbiah Elankumaran,Jianhua Xing +8 more
TL;DR: Experimental and computational analyses identify multiple cell populations during the epithelial-to-mesenchymal transition and provide experimental confirmation for a model of cascading switches in phenotypes associated with TGF-β1–induced EMT of MCF10A cells that involves two double-negative feedback loops.
Journal ArticleDOI
Circulating Plasma MiR-141 Is a Novel Biomarker for Metastatic Colon Cancer and Predicts Poor Prognosis
Hanyin Cheng,Lina Zhang,David Cogdell,Hong Zheng,Aaron J. Schetter,Matti Nykter,Curtis C. Harris,Kexin Chen,Stanley R. Hamilton,Wei Zhang +9 more
TL;DR: It is proposed that plasma miR-141 may represent a novel biomarker that complements CEA in detecting colon cancer with distant metastasis and that high levels of miR -141 in plasma were associated with poor prognosis.
Journal ArticleDOI
Let-7 and miR-200 microRNAs: Guardians against pluripotency and cancer progression
TL;DR: It is proposed that steps of tumor progression can be viewed as a continuum of progressive dedifferentiation (EMT) with a cell at the endpoint that has stem cell-like properties and steps of this process are driven by specific changes in the expression of let-7 and miR-200 family members.
Journal ArticleDOI
miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition
Alessandra Magenta,Chiara Cencioni,Pasquale Fasanaro,Germana Zaccagnini,Simona Greco,Gianluca Sarra-Ferraris,Angelo Antonini,Fabio Martelli,Maurizio C. Capogrossi +8 more
TL;DR: ROS induce miR-200c and other miR -200 family members; the ensuing downmodulation of ZEB1 has a key role in ROS-induced apoptosis and senescence.
References
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