在去势抵抗性前列腺癌细胞中，EZH2 致癌活性是独立于 Polycomb 的。
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent.
机构信息
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
出版信息
Science. 2012 Dec 14;338(6113):1465-9. doi: 10.1126/science.1227604.
Abstract
Epigenetic regulators represent a promising new class of therapeutic targets for cancer. Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.
摘要
表观遗传调控因子是癌症治疗的一个很有前途的新靶点。EZH2（多梳抑制复合物 2 的一个亚基）通过其组蛋白甲基转移酶活性沉默基因表达。我们发现，EZH2 在去势抵抗性前列腺癌细胞中的致癌功能与其作为转录抑制剂的作用无关。相反，它涉及 EZH2 作为包括雄激素受体在内的关键转录因子的共激活剂的能力。这种功能转换依赖于 EZH2 的磷酸化，并且需要完整的甲基转移酶结构域。因此，针对 EZH2 的非 PRC2 功能可能对治疗转移性、激素难治性前列腺癌具有治疗效果。
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