PMID- 34052835
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210616
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 7
IP  - 1
DP  - 2021 May 29
TI  - Simultaneously targeting SOAT1 and CPT1A ameliorates hepatocellular carcinoma by 
      disrupting lipid homeostasis.
PG  - 125
LID - 10.1038/s41420-021-00504-1 [doi]
LID - 125
AB  - 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.
FAU - Ren, Meiling
AU  - Ren M
AD  - Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular 
      Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan Province, 610041, China.
FAU - Xu, Huanji
AU  - Xu H
AD  - Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular 
      Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan Province, 610041, China.
FAU - Xia, Hongwei
AU  - Xia H
AD  - Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular 
      Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan Province, 610041, China.
FAU - Tang, Qiulin
AU  - Tang Q
AD  - Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular 
      Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan Province, 610041, China.
FAU - Bi, Feng
AU  - Bi F
AD  - Department of Abdominal Oncology, Cancer Center and Laboratory of Molecular 
      Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu, 
      Sichuan Province, 610041, China. bifeng@scu.edu.cn.
LA  - eng
GR  - 81872020/National Natural Science Foundation of China (National Science 
      Foundation of China)/
PT  - Journal Article
DEP - 20210529
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC8164629
COIS- The authors declare no competing interests.
EDAT- 2021/05/31 06:00
MHDA- 2021/05/31 06:01
PMCR- 2021/05/29
CRDT- 2021/05/30 21:05
PHST- 2021/01/20 00:00 [received]
PHST- 2021/05/03 00:00 [accepted]
PHST- 2021/04/19 00:00 [revised]
PHST- 2021/05/30 21:05 [entrez]
PHST- 2021/05/31 06:00 [pubmed]
PHST- 2021/05/31 06:01 [medline]
PHST- 2021/05/29 00:00 [pmc-release]
AID - 10.1038/s41420-021-00504-1 [pii]
AID - 504 [pii]
AID - 10.1038/s41420-021-00504-1 [doi]
PST - epublish
SO  - Cell Death Discov. 2021 May 29;7(1):125. doi: 10.1038/s41420-021-00504-1.