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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.
摘要：
代谢重编程在支持肿瘤生长中起重要作用。然而,对促进癌症转移的代谢改变知之甚少。在这项研究中,我们确定酰基辅酶A硫酯酶12（ACOT12）是肝细胞癌（HCC）转移的关键参与者。ACOT12在HCC组织中的表达明显下调，与HCC转移和HCC患者的低生存率密切相关。功能增益和功能丧失研究表明，ACOT12在体外和体内均能抑制HCC转移。进一步的机制研究表明，ACOT12调节HCC细胞中的乙酰辅酶A水平和组蛋白乙酰化，并且ACOT12的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。一起来看,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可能是一个预后标志物和潜在的抗HCC转移治疗靶点.
