Cell Plasticity & Cancer - Inserm U908, University of Lille Bâtiment SN3, Cité Scientifique, F-59655 Villeneuve d'Ascq, France ; Interdisciplinary Research Institute - CNRS USR3078/University of Lille Parc de la Haute Borne, 50 avenue de Halley, F-59658 Villeneuve d'Ascq, France.
Cell Plasticity & Cancer - Inserm U908, University of Lille Bâtiment SN3, Cité Scientifique, F-59655 Villeneuve d'Ascq, France.
Am J Transl Res. 2015 Feb 15;7(2):175-93. eCollection 2015.
EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization. Numerous evidences show that EZH2 plays a critical role in cancer initiation, progression and metastasis, as well as in cancer stem cell biology. Indeed, EZH2 dysregulation alters gene expression programs in various cancer types. The molecular mechanisms responsible for EZH2 alteration appear to be diverse and depending on the type of cancer. Furthermore, accumulating evidences indicate that EZH2 could also act as a PRC2-independent transcriptional activator in cancer. In this review, we address the current understanding of the oncogenic role of EZH2, including the mechanisms of EZH2 dysregulation in cancer and progresses in therapeutic approaches targeting EZH2.
EZH2 是 Polycomb 抑制复合物 2（PRC2）的催化亚基，它催化组蛋白 H3 赖氨酸 27 的甲基化（H3K27me），并通过局部染色质重排介导靶基因的沉默。大量证据表明，EZH2 在癌症的发生、进展和转移以及癌症干细胞生物学中起着关键作用。事实上，EZH2 的失调改变了各种癌症类型中的基因表达程序。导致 EZH2 改变的分子机制似乎多种多样，取决于癌症的类型。此外，越来越多的证据表明，EZH2 也可以在癌症中作为 PRC2 非依赖性转录激活因子发挥作用。在这篇综述中，我们讨论了 EZH2 的致癌作用的最新认识，包括 EZH2 失调在癌症中的机制以及针对 EZH2 的治疗方法的进展。
