TY - JOUR
T1 - Sox4 Is a Master Regulator of Epithelial-Mesenchymal Transition by Controlling Ezh2 Expression and Epigenetic Reprogramming
AU - Tiwari, Neha
AU - Tiwari, Vijay K.
AU - Waldmeier, Lorenz
AU - Balwierz, Piotr J.
AU - Arnold, Phil
AU - Pachkov, Mikhail
AU - Meyer-Schaller, Nathalie
AU - Schübeler, Dirk
AU - vanNimwegen, Erik
AU - Christofori, Gerhard
PY - 2013/6/10
Y1 - 2013/6/10
N2 - 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 invitro and for primary tumor growth and metastasis invivo. 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. © 2013 Elsevier Inc.
AB - 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 invitro and for primary tumor growth and metastasis invivo. 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. © 2013 Elsevier Inc.
UR - http://www.mendeley.com/research/sox4-master-regulator-epithelialmesenchymal-transition-controlling-ezh2-expression-epigenetic-reprog
U2 - 10.1016/j.ccr.2013.04.020
DO - 10.1016/j.ccr.2013.04.020
M3 - Article
SN - 1535-6108
VL - 23
SP - 768
EP - 783
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -
