Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming.

Tiwari N, Tiwari VK, Waldmeier L, Balwierz PJ, Arnold P, Pachkov M, Meyer-Schaller N, Schübeler D, van Nimwegen E, Christofori G
Cancer Cell. 2013 23 (6): 768-83

PMID: 23764001 · DOI:10.1016/j.ccr.2013.04.020

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Animals Cell Line Cell Movement Cell Survival Enhancer of Zeste Homolog 2 Protein Epigenesis, Genetic Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic Histones Humans Mammary Neoplasms, Experimental MCF-7 Cells Methylation Mice Neoplasm Metastasis Polycomb Repressive Complex 2 Promoter Regions, Genetic SOXC Transcription Factors Transcription, Genetic

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