A specific cholesterol metabolic pathway is established in a subset of HCCs for tumor growth
文献类型：期刊论文
| 作者 | Lu, M; Hu, XH; Li, Q; Xiong, Y; Hu, GJ; Xu, JJ; Zhao, XN; Wei, XX; Chang, CCY; Liu, YK |
| 刊名 | JOURNAL OF MOLECULAR CELL BIOLOGY
 |
| 出版日期 | 2013 |
| 卷号 | 5期号:6页码:404-415 |
| 关键词 | ACAT2 CpG methylation oxysterol secretion inhibition of tumor growth HCC |
| 通讯作者 | Song, BL (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China.,blsong@sibcb.ac.cn ; blli@sibcb.ac.cn |
| 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. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | LOW-DENSITY-LIPOPROTEIN ; ACYLTRANSFERASE INHIBITOR AVASIMIBE ; OXYSTEROL-INDUCED APOPTOSIS ; BILE-ACID SYNTHESIS ; HEPATOCELLULAR-CARCINOMA ; ACYL-COA ; ATHEROSCLEROTIC LESIONS ; GENE-EXPRESSION ; HEPG2 CELLS ; HUMAN LIVER |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000330715900006 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/399]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Lu, M,Hu, XH,Li, Q,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, M.,Hu, XH.,Li, Q.,Xiong, Y.,Hu, GJ.,...&Li, BL.(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, M,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. |
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