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

doi:10.1016/j.ccell.2020.05.022

	SETD2 Restricts Prostate Cancer Metastasis by Integrating EZH2 and AMPK Signaling Pathways
	Yuan, Huairui 3; Han, Ying 3; Wang, Xuege 3; Li, Ni 3; Liu, Qiuli 2; Yin, Yuye 5; Wang, Hanling 3; Pan, Lulu 6; Li, Li 7; Song, Kun 1
刊名	CANCER CELL
	2020-09-14
卷号	38 期号:3 页码:350-+
ISSN号	1535-6108
DOI	10.1016/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.
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关键词	HISTONE H3 METHYLATION ; ENERGY SENSOR ; MURINE PROSTATE ; IN-VIVO ; POLYCOMB ; METFORMIN ; MUTATIONS ; PRC2 ; PROTEINS ; IDENTIFICATION
WOS研究方向	Oncology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000581017400013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291504]
专题	中国科学院上海药物研究所
通讯作者	Wang, Xiaoming; Jiang, Jun; Qin, Jun
作者单位	1.Shanghai Jiao Tong Univ, Renji Hosp, State Key Lab Oncogenes & Related Genes, Sch Med, Shanghai 200127, Peoples R China 2.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China 3.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 4.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 5.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 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.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
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-+.