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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The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis
TL;DR: The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGF β signaling pathway without affecting its tumor suppressive effects are highlighted.
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miR-200 Enhances Mouse Breast Cancer Cell Colonization to Form Distant Metastases
Derek M. Dykxhoorn,Yichao Wu,Huangming Xie,Fengyan Yu,Fengyan Yu,Ashish Lal,Fabio Petrocca,Denis Martinvalet,Erwei Song,Bing Lim,Bing Lim,Judy Lieberman +11 more
TL;DR: Expression of miR-200, which promotes a mesenchymal to epithelial cell transition (MET) by inhibiting Zeb2 expression, unexpectedly enhances macroscopic metastases in mouse breast cancer cell lines, suggesting that for some tumors, tumor colonization at metastatic sites might be enhanced by MET.
Journal ArticleDOI
Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis
Veronica Davalos,Catia Moutinho,A. Villanueva,Raquel Boque,Paula Silva,Fátima Carneiro,Manel Esteller,Manel Esteller +7 more
TL;DR: It is discovered that the miR-200 epigenetic silencing is not an static and fixed process but it can be shifted to hypermethylated or unmethylated 5′-CpG island status corresponding to the EMT and MET phenotypes, respectively.
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Cancer Stem Cells and Epithelial-to-Mesenchymal Transition (EMT)-Phenotypic Cells: Are They Cousins or Twins?
TL;DR: The state-of-the authors'-knowledge regarding the molecular similarities between cancer stem-like cells or CSCs and EMT-phenotypic cells that are associated with tumor aggressiveness focusing on solid tumors are summarized.
Journal ArticleDOI
MicroRNA-regulated pathways associated with endometriosis.
E. Maria C. Ohlsson Teague,Kylie H. Van der Hoek,Mark B. Van der Hoek,Naomi Perry,Prabhath Wagaarachchi,Sarah A. Robertson,Cristin G. Print,Louise Hull +7 more
TL;DR: Functional analysis suggested that the 673 miRNA targets constitute molecular pathways previously associated with endometriosis, including c-Jun, CREB-binding protein, protein kinase B (Akt), and cyclin D1 (CCND1) signaling.
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