The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis.
The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis.
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脂肪酸受体 CD36 通过激活 Src/PI3K/AKT 轴依赖性有氧糖酵解促进 HCC 进展
DOI：
10.1038/s41419-021-03596-w
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发表时间：
2021-03-26
影响因子：
9
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Luo X;Zheng E;Wei L;Zeng H;Qin H;Zhang X;Liao M;Chen L;Zhao L;Ruan XZ;Yang P;Chen Y
代谢重编程是癌症的一个新标志，但在肝细胞癌发生（HCC）中的定义仍不明确。脂肪酸受体CD 36与肝脏中的脂质和葡萄糖代谢相关。然而，CD 36在HCC进展中代谢重编程的作用仍有待阐明。在本研究中，我们发现，CD 36是高表达的人肝癌组织相比，非肿瘤肝组织。CD 36过表达促进HCC细胞的增殖、迁移、侵袭和体内肿瘤生长，而沉默CD 36则具有相反的作用。通过细胞代谢表型分析，CD 36表达与细胞外酸化率（糖酵解的一种测量）而不是耗氧率呈正相关。进一步的实验证实，CD 36的过表达导致糖酵解通量和乳酸产生增加。CD 36通过激活Src/PI 3 K/AKT信号轴诱导mTOR介导的致癌糖酵解。用PI 3 K/AKT/mTOR抑制剂预处理HCC细胞在很大程度上阻断了CD 36的促肿瘤作用。我们的研究结果表明，CD 36通过Src/PI 3 K/AKT/mTOR信号通路介导有氧糖酵解，对HCC的生长和转移发挥刺激作用。
Metabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.
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