Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by disrupting lipid homeostasis.
Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by disrupting lipid homeostasis.
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同时靶向 SOAT1 和 CPT1A 通过破坏脂质稳态来改善肝细胞癌
DOI：
10.1038/s41420-021-00504-1
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发表时间：
2021-05-29
影响因子：
7
通讯作者：
Bi F
中科院分区：
文献类型：
--
作者：
Ren M;Xu H;Xia H;Tang Q;Bi F
Lipid homeostasis plays a fundamental role in the development of hepatocellular carcinoma (HCC). However, the mechanisms that regulate lipid homeostasis to avoid lipotoxicity in HCC remain elusive. Here, we found high-fat diet (HFD) improved the expression of sterol o-acyltransferase1 (SOAT1) and carnitine palmitoyltransferase 1A (CPT1A) in diethylnitrosamine-induced HCC. Bioinformatic analysis showed that SOAT1-mediated fatty acid storage and CPT1A-mediated fatty acids oxidation (FAO) formed a double-negative feedback loop in HCC. We verified that SOAT1 inhibition enhanced CPT1A protein, which shuttled the released fatty acids into the mitochondria for oxidation in vivo and in vitro. Besides, we further confirmed that CPT1A inhibition converted excess fatty acids into lipid drops by SOAT1 in vitro. Simultaneously targeting SOAT1 and CPT1A by the small-molecule inhibitors avasimibe and etomoxir had synergistic anticancer efficacy in HCC in vitro and in vivo. Our study provides new mechanistic insights into the regulation of lipid homeostasis and suggests the combination of avasimibe and etomoxir is a novel strategy for HCC treatment.
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DOI：
10.1186/s40880-018-0301-4
发表时间：
2018-05-21
期刊：
Cancer communications (London, England)
影响因子：
--
作者：
Cheng C;Geng F;Cheng X;Guo D
通讯作者：
Guo D
影响因子：
20.3
作者：
Ricciardi, Maria Rosaria;Mirabilii, Simone;Tafuri, Agostino
通讯作者：
Tafuri, Agostino
影响因子：
8
作者：
Buzzai, M;Bauer, DE;Thompson, CB
通讯作者：
Thompson, CB
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
5.2
作者：
Oh YS;Bae GD;Baek DJ;Park EY;Jun HS
通讯作者：
Jun HS