The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability

doi:10.1016/j.molcel.2021.04.009

	The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability
	Pan, Qiang 4,5; Zhong, Shanshan 6; Wang, Hanling 4,5; Wang, Xuege 4,5; Li, Ni 4,5; Li, Yaqi 7,8; Zhang, Guoying 4,5; Yuan, Huairui 4,5; Lian, Yannan 4,5; Chen, Qilong 4,5
刊名	MOLECULAR CELL
	2021-07-01
卷号	81 期号:13 页码:2736-+
ISSN号	1097-2765
DOI	10.1016/j.molcel.2021.04.009
通讯作者	Peng, Junjie(pengjj67@hotmail.com) ; Xiao, Yichuan(ycxiao@sibs.ac.cn) ; Qin, Jun(qinjun@sibs.ac.cn)
英文摘要	Cholesterol metabolism is tightly associated with colorectal cancer (CRC). Nevertheless, the clinical benefit of statins, the inhibitor of cholesterol biogenesis mevalonate (MVA) pathway, is inconclusive, possibly because of a lack of patient stratification criteria. Here, we describe that YAP-mediated zinc finger MYND-type containing 8 (ZMYND8) expression sensitizes intestinal tumors to the inhibition of the MVA pathway. We show that the oncogenic activity of YAP relies largely on ZMYND8 to enhance intracellular de novo cholesterol biogenesis. Disruption of the ZMYND8-dependent MVA pathway greatly restricts the self-renewal capacity of Lgr5(+) intestinal stem cells (ISCs) and intestinal tumorigenesis. Mechanistically, ZMYND8 and SREBP2 drive the enhancer-promoter interaction to facilitate the recruitment of Mediator complex, thus up regulating MVA pathway genes. Together, our results establish that the epigenetic reader ZMYND8 endows YAP-high intestinal cancer with metabolic vulnerability.
资助项目	National Key Research and Development Program of China[2018YFA0902700] ; National Natural Science Foundation of China Projects[81825018] ; National Natural Science Foundation of China Projects[81773121] ; National Natural Science Foundation of China Projects[81802818] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; Chinese Academy of Sciences[QYZDB-SSW-SMC052] ; Program of Shanghai Academic/Technology Research Leader[19XD1424300] ; Initiative Postdocs Supporting Program of the Ministry of Human Resources and Social Security (MOHRSS) ; National Postdoc Management Committee[bx201800247]
WOS关键词	SET ENRICHMENT ANALYSIS ; STEM-CELLS ; WEB SERVER ; TRANSCRIPTION ; SREBP ; PROTEIN ; EXPRESSION ; INTERPLAY ; ZMYND8 ; TAZ
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000672572800008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298271]
专题	中国科学院上海药物研究所
通讯作者	Peng, Junjie; Xiao, Yichuan; Qin, Jun
作者单位	1.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Child, Dept Obstet Gynecol & Pediat, Dept Obstet Gynecol & Pediat,Minist Educ, 20 Renmin South Rd, Chengdu 610041, Peoples R China 4.Shanghai Jiao Tong Univ, Shanghai Inst Nutr & Hlth, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Tissue Microenvironm & Tumor,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China 5.Chinese Acad Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 6.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, 320 Yueyang Rd, Shanghai 200031, Peoples R China 7.Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai 200032, Peoples R China 8.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
推荐引用方式 GB/T 7714	Pan, Qiang,Zhong, Shanshan,Wang, Hanling,et al. The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability[J]. MOLECULAR CELL,2021,81(13):2736-+.
APA	Pan, Qiang.,Zhong, Shanshan.,Wang, Hanling.,Wang, Xuege.,Li, Ni.,...&Qin, Jun.(2021).The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability.MOLECULAR CELL,81(13),2736-+.
MLA	Pan, Qiang,et al."The ZMYND8-regulated mevalonate pathway endows YAP-high intestinal cancer with metabolic vulnerability".MOLECULAR CELL 81.13(2021):2736-+.