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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
MicroRNA expression and its implications for the diagnosis and therapeutic strategies of breast cancer
TL;DR: Exploitation of the therapeutic potential of RNA interference will be an important task and achieved through the further understanding of the mechanisms of gene regulation by miRNAs.
Journal ArticleDOI
Prognostic significance of Zinc finger E-box binding homeobox 1 (ZEB1) expression in cancer cells and cancer-associated fibroblasts in pancreatic head cancer.
Peter Bronsert,Ilona Kohler,Sylvia Timme,Selina Kiefer,Martin Werner,Oliver Schilling,Yogesh K. Vashist,Frank Makowiec,Thomas Brabletz,Ulrich T. Hopt,Dirk Bausch,B Kulemann,Tobias Keck,Ulrich F. Wellner +13 more
TL;DR: Stromal Z EB1 expression is identified for the first time as an independent predictor of survival after resection of PDAC, suggesting that therapies targeting ZEB1 and its downstream pathways could hit both cancer cells and supporting cancer-associated fibroblasts.
Journal ArticleDOI
Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis.
Marjon A. Smit,Daniel S. Peeper +1 more
TL;DR: Zeb1 is required for TrkB-induced EMT in epithelial cells, as RNAi-mediated knockdown of Zeb1 reverted the morphological changes induced by TrkB, including metastasis.
Journal ArticleDOI
MicroRNAs as Novel Biomarkers in Colorectal Cancer.
Sonja Hrašovec,Damjan Glavač +1 more
TL;DR: This review summarizes the recent findings of the clinicopathological relevance that miRNAs have in CRC initiation, development, and progress, highlighting their potential diagnostic, prognostic, and therapeutic use in CRC, focusing on the group of microsatellite instable and theGroup of hypermethylated CRCs, as well as discussing future prospects.
Journal ArticleDOI
MicroRNAs in colorectal cancer: small molecules with big functions.
Yu Xuan,Huiliang Yang,Linjie Zhao,Wayne Bond Lau,Bonnie Lau,Ning Ren,Yuehong Hu,Tao Yi,Xia Zhao,Shengtao Zhou,Yuquan Wei +10 more
TL;DR: It is hopeful that novel miRNA-based therapeutic strategies may be available for CRC patients in the future because of a remarkable number of miRNAs discovered with implications via incompletely understood mechanisms in CRC.
References
More filters
Journal ArticleDOI
MicroRNAs: Genomics, Biogenesis, Mechanism, and Function
TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal Article
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Journal ArticleDOI
Prediction of Mammalian MicroRNA Targets
TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
Journal ArticleDOI
Complex networks orchestrate epithelial–mesenchymal transitions
TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
Journal ArticleDOI
Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).