Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming

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• 作者：Neha Tiwari¹ ; ⁴ ; Vijay K. Tiwari² ; ⁵ ; Lorenz Waldmeier¹ ; Piotr J. Balwierz³ ; Phil Arnold³ ; Mikhail Pachkov³ ; Nathalie Meyer-Schaller¹ ; Dirk Schü ; beler² ; Erik van Nimwegen³ ; Gerhard Christofori¹ ; ^{gerhard.christofori@unibas.ch}
• 刊名：Cancer Cell
• 出版年：2013
• 出版时间：10 June, 2013
• 年：2013
• 卷：23
• 期：6
• 页码：768-783
• 全文大小：4511 K

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Summary

Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-¦Â-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.