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
Key signalling nodes in mammary gland development and cancer. The Snail1-Twist1 conspiracy in malignant breast cancer progression
TL;DR: In this paper, the role of Epithelial-to-mesenchymal transition (EMT) in normal mammary gland development is discussed and regulatory mechanisms involving newly discovered upstream regulators and microRNAs, the association of EMT with breast cancer stem cells, and the involvement of the tumour microenvironment in breast cancer progression are discussed.
Journal ArticleDOI
MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential.
Manmeet Rawat,Kavita Kadian,Yash Gupta,Anand Kumar,Patrick S. G. Chain,Olga Kovbasnjuk,Suneel Kumar,Gulshan Parasher +7 more
TL;DR: This review provides a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models and describes the role of mi RNA in cell cycle and proliferation, apoptosis, and metastasis.
Journal ArticleDOI
Differential expression of microRNA expression in tamoxifen-sensitive MCF-7 versus tamoxifen-resistant LY2 human breast cancer cells
Tissa T. Manavalan,Yun Teng,Savitri Appana,Susmita Datta,Theodore S. Kalbfleisch,Yong Li,Carolyn M. Klinge +6 more
TL;DR: Microarrays identified miRNAs differentially expressed and 4-hydroxytamoxifen regulated in MCF-7 endocrine-sensitive versus resistant LY2 human breast cancer cells that may be involved in endocrine resistance.
Journal ArticleDOI
MicroRNA-141 Regulates Smad Interacting Protein 1 (SIP1) and Inhibits Migration and Invasion of Colorectal Cancer Cells
TL;DR: It is demonstrated that miR-141 levels correlate inversely with SIP1 protein levels as well as cell migration and invasion of CRC cells.
Journal ArticleDOI
Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model
Jacqueline Banyard,Jacqueline Banyard,Ivy Chung,Ivy Chung,Ivy Chung,Arianne M. Wilson,Guillaume Vetter,Antony Le Béchec,Diane R. Bielenberg,Diane R. Bielenberg,Bruce R. Zetter,Bruce R. Zetter +11 more
TL;DR: This model provides evidence for spontaneous MET in vivo and shows that this cellular plasticity can be mediated through the combined action of miR-424 and themiR-200 family.
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).