Association between EZH2 expression, silencing of tumor suppressors and disease outcome in solid tumors

Cell Cycle. 2016 Sep;15(17):2256-62. doi: 10.1080/15384101.2016.1208872. Epub 2016 Jul 15.

Abstract

EZH2, the main catalytic component of the Polycomb Repressive Complex 2 (PRC2) is apparently upregulated in most solid tumors. Furthermore its expression generally associates with poor prognosis. It was proposed that this correlation reflects a causal event, EZH2 mediating the silencing of key tumor suppressor loci. In contrast, we recently showed that EZH2 is dispensable for solid tumor development and that its elevated expression reflects the abnormally high proliferation rate of cancer cells. Here, we investigate the functional association between EZH2 expression and silencing of key tumor suppressor loci and further illustrate the confounding effect of proliferation on EZH2's association to outcome.

Keywords: EZH2; PRC2; Polycomb; breast; prognosis; prostate; solid tumors; tumor suppressor.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Cell Line, Transformed
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Gene Silencing*
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Models, Biological
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse