A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth

doi:10.1093/jmcb/mjt039

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	A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth
	Lu, Ming 4; Hu, Xi-Han 4; Li, Qin 4; Xiong, Ying 4; Hu, Guang-Jing 4; Xu, Jia-Jia 4; Zhao, Xiao-Nan 4; Wei, Xi-Xiao 4; Chang, Catherine C. Y.1; Liu, Yin-Kun 2
刊名	JOURNAL OF MOLECULAR CELL BIOLOGY
	2013-12
卷号	5 期号:6 页码:404-415
关键词	ACAT2 CpG methylation oxysterol secretion inhibition of tumor growth HCC
ISSN号	1674-2788
DOI	10.1093/jmcb/mjt039
文献子类	Article
英文摘要	The liver plays a central role in cholesterol homeostasis. It exclusively receives and metabolizes oxysterols, which are important metabolites of cholesterol and are more cytotoxic than free cholesterol, from all extrahepatic tissues. Hepatocellular carcinomas (HCCs) impair certain liver functions and cause pathological alterations in many processes including cholesterol metabolism. However, the link between an altered cholesterol metabolism and HCC development is unclear. Human ACAT2 is abundantly expressed in intestine and fetal liver. Our previous studies have shown that ACAT2 is induced in certain HCC tissues. Here, by investigating tissue samples from HCC patients and HCC cell lines, we report that a specific cholesterol metabolic pathway, involving induction of ACAT2 and esterification of excess oxysterols for secretion to avoid cytotoxicity, is established in a subset of HCCs for tumor growth. Inhibiting ACAT2 leads to the intracellular accumulation of unesterified oxysterols and suppresses the growth of both HCC cell lines and their xenograft tumors. Further mechanistic studies reveal that HCC-linked promoter hypomethylation is essential for the induction of ACAT2 gene expression. We postulate that specifically blocking this HCC-established cholesterol metabolic pathway may have potential therapeutic applications for HCC patients.
资助项目	Ministry of Science and Technology of China[2011CB910900] ; Ministry of Science and Technology of China[2009CB919000] ; National Institutes of Health, USA[HL36709] ; National Natural Science Foundation of China[30771233]
WOS关键词	LOW-DENSITY-LIPOPROTEIN ; ACYLTRANSFERASE INHIBITOR AVASIMIBE ; OXYSTEROL-INDUCED APOPTOSIS ; BILE-ACID SYNTHESIS ; HEPATOCELLULAR-CARCINOMA ; ACYL-COA ; ATHEROSCLEROTIC LESIONS ; GENE-EXPRESSION ; HEPG2 CELLS ; HUMAN LIVER
WOS研究方向	Cell Biology
语种	英语
CSCD记录号	CSCD:5004164
出版者	OXFORD UNIV PRESS
WOS记录号	WOS:000330715900006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277343]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物安全性评价中心
通讯作者	Song, Bao-Liang
作者单位	1.Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA; 2.Fudan Univ, Zhong Shan Hosp, Liver Canc Inst, Shanghai 200031, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Lu, Ming,Hu, Xi-Han,Li, Qin,et al. A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth[J]. JOURNAL OF MOLECULAR CELL BIOLOGY,2013,5(6):404-415.
APA	Lu, Ming.,Hu, Xi-Han.,Li, Qin.,Xiong, Ying.,Hu, Guang-Jing.,...&Li, Bo-Liang.(2013).A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth.JOURNAL OF MOLECULAR CELL BIOLOGY,5(6),404-415.
MLA	Lu, Ming,et al."A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth".JOURNAL OF MOLECULAR CELL BIOLOGY 5.6(2013):404-415.