Acetylation of PGK1 Promotes Liver Cancer Cell Proliferation and Tumorigenesis

Acetylation of PGK1 Promotes Liver Cancer Cell Proliferation and Tumorigenesis
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PGK1乙酰化促进肝癌细胞增殖和肿瘤发生

DOI:
10.1002/hep.28887
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发表时间:
2017-02-01
期刊:
影响因子:
13.5
通讯作者:
Gao, Daming
Gao, Daming
中科院分区:
医学1区
文献类型:
--
作者:
Hu, Hongli;Zhu, Wenwei;Gao, Daming

文献摘要

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磷酸甘油酸激酶1(PGK1)是代谢糖酵解途径中的一个重要酶。在本研究中,我们观察到PGK1在肝癌组织中显著过表达,并与肝癌患者的生存期呈负相关。此外,PGK1的缺失显著降低了癌细胞的增殖和肿瘤的发生,表明PGK1在肝癌进展中具有致癌作用。此外,我们还发现PGK1的K323位的乙酰化是促进其酶活性和癌细胞代谢的重要调节机制。我们进一步确定P300/环磷酸腺苷反应元件结合蛋白结合蛋白相关因子(PCAF)和Sirtuin 7是从两个方向调节肝癌细胞K323乙酰化的酶。结论:这些发现表明了PGK1的一种新的调控及其在肝癌进展中的重要作用。(《肝病》2017;65:515-528)。
Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein–binding protein–associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. Conclusion: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515‐528).