The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

作者全名："Luo, Xiaoqing; Zheng, Enze; Wei, Li; Zeng, Han; Qin, Hong; Zhang, Xiaoyu; Liao, Meng; Chen, Lin; Zhao, Lei; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi"

作者地址："[Luo, Xiaoqing; Zheng, Enze; Wei, Li; Zeng, Han; Qin, Hong; Zhang, Xiaoyu; Liao, Meng; Chen, Lin; Zhao, Lei; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Ctr Lipid Res, Chongqing 400016, Peoples R China; [Luo, Xiaoqing; Zheng, Enze; Wei, Li; Zeng, Han; Qin, Hong; Zhang, Xiaoyu; Liao, Meng; Chen, Lin; Zhao, Lei; Ruan, Xiong Z.; Yang, Ping; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Minist Educ,Dept Infect Dis,Key Lab Mol Biol Infe, Chongqing 400016, Peoples R China; [Ruan, Xiong Z.] UCL, Univ Coll London Med Sch, Ctr Nephrol, John Moorhead Res Lab, Royal Free Campus, London NW3 2PF, England"

通信作者："Yang, P; Chen, YX (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Ctr Lipid Res, Chongqing 400016, Peoples R China.; Yang, P; Chen, YX (corresponding author), Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Minist Educ,Dept Infect Dis,Key Lab Mol Biol Infe, Chongqing 400016, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000681173200007

JCR分区：Q1

影响因子：9

年份：2021

卷号：12

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："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."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81873569, 32030054]; National Key R&D Program of China [2018YFC1312700]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2020jcyj-msxmX0205, cstc2020jcyj-zdxmX0007]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K201800401]; Science and Technology Project of Yuzhong District of Chongqing [20190120]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; 111 ProjectMinistry of Education, China - 111 Project [D20028]"

基金资助正文："This study was supported by the National Natural Science Foundation of China (81873569 and Key Program, No. 32030054), the National Key R&D Program of China (2018YFC1312700), the Chongqing Research Program of Basic Research and Frontier Technology (cstc2020jcyj-msxmX0205, cstc2020jcyj-zdxmX0007), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K201800401), the Science and Technology Project of Yuzhong District of Chongqing (20190120), Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University, and the 111 Project (No. D20028)."