ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition.
Cell Metab
; 29(4): 886-900.e5, 2019 04 02.
Article
en En
| MEDLINE
| ID: mdl-30661930
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Acetilcoenzima A
/
Tioléster Hidrolasas
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Carcinoma Hepatocelular
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Transición Epitelial-Mesenquimal
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2019
Tipo del documento:
Article