Regulating Methylation at H3K27: A Trick or Treat for Cancer Cell Plasticity

SIMPLE SUMMARY: Regulation of gene expression is important for appropriate cell development but can also lead to inappropriate cell transformation resulting in cancer. Modification to the proteins that wrap DNA is essential for regulating gene expression. Mutations in the enzymes that modify such proteins are being discovered in many cancers. This review will cover present knowledge of these enzymes as they relate to cancer initiation and progression. ABSTRACT: Properly timed addition and removal of histone 3 lysine 27 tri-methylation (H3K27me3) is critical for enabling proper differentiation throughout all stages of development and, likewise, can guide carcinoma cells into altered differentiation states which correspond to poor prognoses and treatment evasion. In early embryonic stages, H3K27me3 is invoked to silence genes and restrict cell fate. Not surprisingly, mutation or altered functionality in the enzymes that regulate this pathway results in aberrant methylation or demethylation that can lead to malignancy. Likewise, changes in expression or activity of these enzymes impact cellular plasticity, metastasis, and treatment evasion. This review focuses on current knowledge regarding methylation and de-methylation of H3K27 in cancer initiation and cancer cell plasticity.