ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition
ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition
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ACOT12 依赖性乙酰辅酶 A 改变通过表观遗传诱导上皮间质转化驱动肝细胞癌转移
DOI：
10.1016/j.cmet.2018.12.019
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发表时间：
2019-04-02
期刊：
影响因子：
29
通讯作者：
Qin, Lun-Xiu
中科院分区：
文献类型：
--
作者：
Lu, Ming;Zhu, Wen-Wei;Qin, Lun-Xiu
代谢重编程在支持肿瘤生长中起着重要作用。然而，人们对促进癌症转移的代谢改变知之甚少。在这项研究中，我们发现酰基辅酶a硫酯酶12 （ACOT12）在肝细胞癌（HCC）转移中起关键作用。ACOT12在HCC组织中表达显著下调，与HCC转移和HCC患者生存不良密切相关。获得和丧失功能的研究表明，ACOT12在体外和体内都抑制HCC转移。进一步的机制研究表明，ACOT12调节HCC细胞乙酰辅酶a水平和组蛋白乙酰化，ACOT12下调通过表观遗传诱导TWIST2表达和促进上皮-间质转化促进HCC转移。综上所述，我们的研究结果将乙酰辅酶a的改变与HCC转移联系起来，并暗示ACOT12可能是一种预后标志物和对抗HCC转移的潜在治疗靶点。
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 lossof-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.