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Sox4 is a master regulator of epithelial-mesenchymal transition by controlling ezh2 expression and epigenetic reprogramming

Tiwari, N. and Tiwari, V. K. and Waldmeier, L. and Balwierz, P. J. and Arnold, P. and Pachkov, M. and Meyer-Schaller, N. and Schubeler, D. and van Nimwegen, E. and Christofori, G.. (2013) Sox4 is a master regulator of epithelial-mesenchymal transition by controlling ezh2 expression and epigenetic reprogramming. Cancer cell, Vol. 23, H. 6. pp. 768-783.

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Official URL: http://edoc.unibas.ch/dok/A6165042

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Abstract

Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (van Nimwegen)
03 Faculty of Medicine > Departement Biomedizin > Division of Biochemistry and Genetics > Tumor Biology (Christofori)
UniBasel Contributors:van Nimwegen, Erik and Christofori, Gerhard M.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:1535-6108
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Apr 2015 09:13
Deposited On:13 Sep 2013 07:56

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