中国科学院上海营养与健康研究所秦骏研究组、重庆军医大学大坪医院江军研究组、南京医科大学王晓明研究组等研究人员合作发现，SETD2通过整合EZH2和AMPK信号通路来限制前列腺癌的转移。该项研究成果于2020年7月2日在线发表在《癌细胞》杂志上。

研究人员发现，SETD2通过其底物EZH2延迟前列腺癌（PCa）转移。研究人员表明，SETD2甲基化EZH2，从而促进EZH2降解。SETD2缺失会引起Polycomb抑制的染色质状态，进而使细胞能够获得转移性状。相反，携带无法甲基化的EZH2突变体或者与EZH2结合缺陷的SETD2突变体的小鼠会产生转移性PCa。此外，研究人员发现二甲双胍刺激的AMPK信号会影响FOXO3来刺激SETD2表达。

总之，这些结果表明，SETD2-EZH2信号轴整合了代谢和表观遗传信号，进而限制PCa的转移。

据悉，SETD2介导的H3K36me3的水平与EZH2催化的H3K27me3的水平成反比。然而，尚不清楚这两种酶活性是否在分子上有关联。 

附：英文原文

Title: SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways

Author: Huairui Yuan, Ying Han, Xuege Wang, Ni Li, Qiuli Liu, Yuye Yin, Hanling Wang, Lulu Pan, Li Li, Kun Song, Tong Qiu, Qiang Pan, Qilong Chen, Guoying Zhang, Yi Zang, Minjia Tan, Jian Zhang, Qintong Li, Xiaoming Wang, Jun Jiang, Jun Qin

Issue&Volume: 2020-07-02

Abstract: The level of SETD2-mediated H3K36me3 is inversely correlated with that of EZH2-catalyzedH3K27me3. Nevertheless, it remains unclear whether these two enzymatic activitiesare molecularly intertwined. Here, we report that SETD2 delays prostate cancer (PCa)metastasis via its substrate EZH2. We show that SETD2 methylates EZH2 which promotesEZH2 degradation. SETD2 deficiency induces a Polycomb-repressive chromatin state thatenables cells to acquire metastatic traits. Conversely, mice harboring nonmethylatedEZH2 mutant or SETD2 mutant defective in binding to EZH2 develop metastatic PCa. Furthermore,we identify that metformin-stimulated AMPK signaling converges at FOXO3 to stimulateSETD2 expression. Together, our results demonstrate that the SETD2-EZH2 axis integratesmetabolic and epigenetic signaling to restrict PCa metastasis.

DOI: 10.1016/j.ccell.2020.05.022

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30272-5