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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PKCα Modulates Epithelial-to-Mesenchymal Transition and Invasiveness of Breast Cancer Cells Through ZEB1.
María Candelaria Llorens,Fabiana Alejandra Rossi,Iris Alejandra García,Iris Alejandra García,Mariana Cooke,Martín Carlos Abba,Cynthia Lopez-Haber,Laura Barrio-Real,Maria Victoria Vaglienti,Maria Victoria Vaglienti,Mario Rossi,Mario Rossi,José Luis Bocco,José Luis Bocco,Marcelo G. Kazanietz,Gastón Soria,Gastón Soria +16 more
TL;DR: PKCα-mediated downregulation of ZEB1 recapitulates the inhibition of mesenchymal phenotypes, including inhibition in cell migration and invasiveness, and unveil an unforeseen regulatory pathway comprising PKCα and Z EB1 that promotes the activation of the EMT in breast cancer cells.
Journal ArticleDOI
Co-optation of Tandem DNA Repeats for the Maintenance of Mesenchymal Identity
Chiara Balestrieri,Gabriele Alfarano,Marta Milan,Valentina Tosi,Elena Prosperini,Paola Nicoli,Andrea Palamidessi,Giorgio Scita,Giuseppe R. Diaferia,Gioacchino Natoli +9 more
TL;DR: It is demonstrated that the high density of identical motifs in TRs can make them suitable platforms for recruitment of transcriptional repressors, thus promoting their exaptation into pre-existing cis-regulatory networks.
Journal ArticleDOI
Regulatory effects of lncRNA ATB targeting miR-200c on proliferation and apoptosis of colorectal cancer cells.
TL;DR: The lncRNA ATB/miR‐200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC.
Journal ArticleDOI
Long non-coding RNA (lncRNA) and epithelial-mesenchymal transition (EMT) in colorectal cancer: a systematic review.
Stephen J. O'Brien,Campbell Bishop,Jacob Hallion,Casey Fiechter,Katharina M Scheurlen,Mason Paas,James R. Burton,Susan Galandiuk +7 more
TL;DR: In this article, a systematic review of cancer metastasis development in colon cancer is presented, where Epithelial-mesenchymal transition (EMT) is a major process in tumor metastasis.
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53BP1 suppresses epithelial-mesenchymal transition by downregulating ZEB1 through microRNA-200b/429 in breast cancer.
TL;DR: It is suggested that 53BP1 functioned as a tumor suppressor gene by its novel negative control of EMT through regulating the expression of miR‐200b/429 and their target gene ZEB1.
References
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