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

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.

The Sound of Silence: How Silenced Chromatin Orchestrates the Repair of Double-Strand Breaks

“…Although f-Het covers a substantial part of the genome, it remains relatively understudied in its response to DSBs. Since f-Het is important in many biological processes, such as X-chromosome inactivation in female mammals, genomic imprinting, stem cell maintenance, and cell differentiation, it is not surprising that polycomb misregulation can lead to diseases such as cancer [ 123 ]. It is, therefore, essential to understand how this silenced state is maintained during the repair of DSBs.…”

Histone demethylase KDM6B inhibits breast cancer metastasis by regulating Wnt/β‐catenin signaling

“…KDM6B, a member of Jumonji domain‐containing proteins, acts as a histone demethylase and is an important regulator in multiple cellular processes, such as cell development, differentiation, senescence and inflammation. More importantly, a large body of data has shown the association of KDM6B abnormality with tumor progression [ 2 ]. Our previous study also showed that KDM6B inhibited the stem cell‐like properties of breast cancer by inhibiting the expression of OCT4.…”

“…Lysine‐specific demethylase 6B (KDM6B), also known as Jumonji domain‐containing protein 3, is a member of the histone demethylases. It specifically catalyzes the removal of the trimethyl group from H3K27 lysine residue to active chromatin conformation [ 2 , 3 ]. It has been shown that KDM6B plays essential roles in development, differentiation, cell senescence and inflammation [ 4 , 5 , 6 ].…”

EZH2 and KDM6B Expressions Are Associated with Specific Epigenetic Signatures during EMT in Non Small Cell Lung Carcinomas

“…These data confirmed that the modulation (increase or decrease) of expression of each enzyme promoted EMT. Das and Taube [26] indeed highlighted the difficulty of addressing the precise contribution of these enzymes in a recent review.…”