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

Neha Tiwari1, Vijay K Tiwari, Lorenz Waldmeier

  • 1Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.

Cancer Cell
|June 15, 2013
PubMed

Insights

Transcription factor Sox4 drives epithelial-mesenchymal transition (EMT) and metastasis by regulating Ezh2, an epigenetic modifier. This Sox4-Ezh2 axis is crucial for tumor growth and patient survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Gene expression profiling identified upregulated Sox4 during TGF-β-induced epithelial-mesenchymal transition (EMT) in breast epithelial cells.
  • Sox4 is essential for EMT, cell survival, tumor growth, and metastasis in vivo.

Purpose of the Study:

  • To investigate the role of Sox4 in regulating EMT and its downstream targets.
  • To elucidate the mechanism by which Sox4 controls EMT and its clinical implications.

Main Methods:

  • Gene expression profiling to identify Sox4.
  • In vitro and in vivo experiments to assess Sox4's role in EMT, cell survival, and metastasis.
  • Analysis of Ezh2 regulation by Sox4 and its impact on H3K27me3 marks.

Main Results:

  • Sox4 directly regulates Ezh2, a histone methyltransferase involved in gene repression.
  • Ezh2 ablation inhibits EMT, while its forced expression rescues EMT in Sox4-deficient cells.
  • Ezh2-mediated H3K27me3 marks on EMT genes form an epigenetic signature predicting patient survival.

Conclusions:

  • Sox4 is a master regulator of EMT, controlling the expression of the epigenetic modifier Ezh2.
  • The Sox4-Ezh2 pathway is critical for breast cancer progression and metastasis.
  • An epigenetic signature involving Ezh2-mediated H3K27me3 marks can predict patient survival.

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