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Review
. 2018 Mar 9:6:10.
doi: 10.1186/s40364-018-0122-2. eCollection 2018.

Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential

Lu Gan #  1   2   3 , Yanan Yang #  1 , Qian Li  2   3 , Yi Feng  2   3 , Tianshu Liu  2   3 , Weijian Guo  1   2
Affiliations
Review

Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential

Lu Gan et al. Biomark Res. .

Abstract

Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells. The tumor suppressive effects of EZH2 are also identified. What is more, EZH2 has decisive roles in immune cells (for example, T cells, NK cells, dendritic cells and macrophages), which are essential components in tumor microenvironment. In this review, we aim to discuss the molecular functions of EZH2, highlight recent findings regarding the physiological functions and related regulation of EZH2 in cancer pathogenesis. Furthermore, we summarized and updated the emerging roles of EZH2 in tumor immunity, and current pre-clinical and clinical trials of EZH2 inhibitors in cancer therapy.

Keywords: Cancer; EZH2; Epigenetic; Histone H3 Lys27 trimethylation; Polycomb repressive complex.

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Conflict of interest statement

Not applicable.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The action modes of EZH2. (1) EZH2 catalyzes H3K27me3 dependent on PCR2, which contributes to transcriptional silencing. (2) EZH2 is also capable of methylating several non-histone protein substrates (e.g. STAT3, GATA4, talin, and RORα), which contributes to both transcriptional silencing and transcriptional activation. 3) EZH2 also has a PRC2-independent role in transcriptional activation, acting as co-activator for transcription factors, such as AR-associated complex, NF-κB signaling, TCF/β-catenin and PCNA, and β-catenin and ERα
Fig. 2
Fig. 2
The physiological functions and related regulation of EZH2 in cancer pathogenesis. The EZH2 expression and activity in cancer cells is regulated at genetic, transcriptional, post-transcriptional and post-translational levels, which leads to diverse functions of EZH2. EZH2, mediating gene transcriptional silencing and activation, promotes cell survival, proliferation, epithelial to mesenchymal, invasionand drug resistance of cancer cells. The tumor suppressive effects of EZH2 are also identified in several cancers, especially T-ALL, pancreatic cancer and clear cell renal carcinoma. What’s more, EZH2 has decisive roles in T and NK cells mediated immune evasion
See this image and copyright information in PMC

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