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Cell Metab. 2019 Apr 2;29(4):886-900.e5. doi: 10.1016/j.cmet.2018.12.019. Epub 2019 Jan 22.

ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition.

Author information

1
Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China. Electronic address: luming@huashan.org.cn.
2
Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China.
3
State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
4
Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
5
Qidong People's Hospital, Jiangsu 226299, China.
6
Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address: qinlx@fudan.edu.cn.

Abstract

Metabolic reprogramming plays an important role in supporting tumor growth. However, little is known about the metabolic alterations that promote cancer metastasis. In this study, we identify acyl-CoA thioesterase 12 (ACOT12) as a key player in hepatocellular carcinoma (HCC) metastasis. The expression of ACOT12 is significantly down-regulated in HCC tissues and is closely associated with HCC metastasis and poor survival of HCC patients. Gain- and loss-of-function studies demonstrate that ACOT12 suppresses HCC metastasis both in vitro and in vivo. Further mechanistic studies reveal that ACOT12 regulates the cellular acetyl-CoA levels and histone acetylation in HCC cells and that down-regulation of ACOT12 promotes HCC metastasis by epigenetically inducing TWIST2 expression and the promotion of epithelial-mesenchymal transition. Taken together, our findings link the alteration of acetyl-CoA with HCC metastasis and imply that ACOT12 could be a prognostic marker and a potential therapeutic target for combating HCC metastasis.

KEYWORDS:

ACOT12; TWIST2; acetyl-CoA; cancer metastasis; epithelial-mesenchymal transition; hepatocellular carcinoma; histone acetylation

PMID:
30661930
DOI:
10.1016/j.cmet.2018.12.019

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