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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Epithelial-Mesenchymal Transitions in Development and Disease
Jean Paul Thiery,Jean Paul Thiery,Hervé Acloque,Ruby Yun-Ju Huang,Ruby Yun-Ju Huang,M. Angela Nieto +5 more
TL;DR: The mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
TL;DR: Recent advances in the understanding of miRNAs in cancer and in other diseases are described and the challenge of identifying the most efficacious therapeutic candidates is discussed and a perspective on achieving safe and targeted delivery of miRNA therapeutics is provided.
Journal ArticleDOI
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
TL;DR: This review will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs, and highlight recent studies implicating the function of TGF-β-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal.
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Regulatory networks defining EMT during cancer initiation and progression
Bram De Craene,Geert Berx +1 more
TL;DR: The EMT-associated reprogramming of cells not only suggests that fundamental changes may occur to several regulatory networks but also that an intimate interplay exists between them.
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MicroRNAs in cancer.
TL;DR: In this paper, the effects of miRNA dysregulation in the cellular pathways that lead to the progressive conversion of normal cells into cancer cells and the potential to develop new molecular miRNA-targeted therapies are discussed.
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Negative regulation of CD4 expression in T cells by the transcriptional repressor ZEB
Thomas Brabletz,Andreas Jung,Falk Hlubek,Christian Löhberg,Johannes Meiler,Ulrike Suchy,Thomas Kirchner +6 more
TL;DR: Evidence is presented that CD4 gene expression is negatively regulated by ZEB, and it is shown that ZEB binds to the 5'E-box in the CD4-3 element of the proximal CD4 enhancer in competition with the transcriptional activators E12 and HEB, thereby reducing CD4 expression on CD4 single-positive but not CD4/CD8 double-positive T cells.