Insulin promotes hepatocarcinoma tumorigenesis by up-regulating PKM2 expression
Insulin promotes hepatocarcinoma tumorigenesis by up-regulating PKM2 expression
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胰岛素通过上调PKM2表达促进肝癌发生
DOI：
10.1016/j.yexcr.2021.112872
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发表时间：
2021
影响因子：
3.7
通讯作者：
Ren Jianlin
中科院分区：
文献类型：
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作者：
Liu Jingjing;Zhi Qiang;Liu Yunpeng;Wang Ying;Chen Linlin;Ke Yuhao;Zeng Lingsu;Wu Xiaoling;Yang Xiaoning;Guleng Bayasi;Liu Hao;Ren Jianlin
胰岛素，作为一种生长因子，会增加患某些癌症的风险。本研究表明，胰岛素通过糖酵解过程中的限速酶丙酮酸激酶M2 （PKM2）促进肝癌细胞的体外和体内增殖。此外，PKM2的表达在翻译后水平上以核孤儿受体tr3依赖的方式被胰岛素上调。此外，胰岛素可以增强PKM2与TR3的相互作用，保护PKM2免受降解。我们的研究结果确定了胰岛素影响癌症代谢的特定机制，从而促进癌症的进展，并有助于更好地理解胰岛素与高胰岛素血症条件下癌症风险增加有关的观察结果。
Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions.