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

文献类型：期刊论文

作者Yuan, Huairui6; Han, Ying6; Wang, Xuege6; Li, Ni6; Liu, Qiuli7; Yin, Yuye2; Wang, Hanling6; Pan, Lulu1; Li, Li3; Song, Kun4
刊名CANCER CELL
出版日期2020-09-14
卷号38期号:3页码:350-+
ISSN号1535-6108
DOI10.1016/j.ccell.2020.05.022
通讯作者Wang, Xiaoming(xmwang@njmu.edu.cn) ; Jiang, Jun(jiangjun_64@163.com) ; Qin, Jun(qinjun@sibs.ac.cn)
英文摘要The level of SETD2-mediated H3K36me3 is inversely correlated with that of EZH2-catalyzed H3K27me3. Nevertheless, it remains unclear whether these two enzymatic activities are molecularly intertwined. Here, we report that SETD2 delays prostate cancer (PCa) metastasis via its substrate EZH2. We show that SETD2 methylates EZH2 which promotes EZH2 degradation. SETD2 deficiency induces a Polycomb-repressive chromatin state that enables cells to acquire metastatic traits. Conversely, mice harboring nonmethylated EZH2 mutant or SETD2 mutant defective in binding to EZH2 develop metastatic PCa. Furthermore, we identify that metformin-stimulated AMPK signaling converges at FOXO3 to stimulate SETD2 expression. Together, our results demonstrate that the SETD2-EZH2 axis integrates metabolic and epigenetic signaling to restrict PCa metastasis.
WOS关键词HISTONE H3 METHYLATION ; ENERGY SENSOR ; MURINE PROSTATE ; IN-VIVO ; POLYCOMB ; METFORMIN ; MUTATIONS ; PRC2 ; PROTEINS ; IDENTIFICATION
资助项目National Key Research and Development Program of China[2018YFA0902700] ; National Natural Science Foundation of China Distinguished Young Scholars Program[81825018] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12000000] ; Chinese Academy of Sciences[QYZDB-SSW-SMC052] ; National Natural Science Foundation of China[81773121] ; National Natural Science Foundation of China[81802818] ; National Natural Science Foundation of China[31970828] ; Program of Shanghai Academic/Technology Research Leader[19XD1424300] ; Initiative Postdocs Supporting Program by MOHRSS ; National Postdoc Management Committee[bx201800247]
WOS研究方向Oncology ; Cell Biology
语种英语
WOS记录号WOS:000581017400013
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/291504]  
专题新药研究国家重点实验室
通讯作者Wang, Xiaoming; Jiang, Jun; Qin, Jun
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Nanjing Med Univ, Key Lab Immune Microenvironm & Dis, Dept Immunol,Collaborat Innovat Ctr Canc Personal, NHC Key Lab Antibody Tech,Dept Microbes & Infect, 101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
3.Shanghai Jiao Tong Univ, Renji Med X Clin Stem Cell Res Ctr, State Key Lab Oncogenes & Related Genes, Sch Med,Affiliated Renji Hosp, Shanghai 200127, Peoples R China
4.Shanghai Jiao Tong Univ, Renji Hosp, State Key Lab Oncogenes & Related Genes, Sch Med, Shanghai 200127, Peoples R China
5.Sichuan Univ, West China Univ Hosp 2, Key Lab Birth Defects & Related Dis Women & Child, Dept Obstet Gynecol & Pediat,Minist Educ, 20 Renmin South Rd, Chengdu 610041, Peoples R China
6.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Tissue Microenvironm & Tumor,Shanghai, 320 Yueyang Rd, Shanghai 200031, Peoples R China
7.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China
推荐引用方式
GB/T 7714		 Yuan, Huairui,Han, Ying,Wang, Xuege,et al. SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways[J]. CANCER CELL,2020,38(3):350-+.
APA Yuan, Huairui.,Han, Ying.,Wang, Xuege.,Li, Ni.,Liu, Qiuli.,...&Qin, Jun.(2020).SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways.CANCER CELL,38(3),350-+.
MLA Yuan, Huairui,et al."SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways".CANCER CELL 38.3(2020):350-+.

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来源：上海药物研究所

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