eprintid: 10125859
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/12/58/59
datestamp: 2021-04-14 11:34:56
lastmod: 2021-09-17 22:26:19
status_changed: 2021-04-14 11:34:56
type: article
metadata_visibility: show
creators_name: Luo, X
creators_name: Zheng, E
creators_name: Wei, L
creators_name: Zeng, H
creators_name: Qin, H
creators_name: Zhang, X
creators_name: Liao, M
creators_name: Chen, L
creators_name: Zhao, L
creators_name: Ruan, XZ
creators_name: Yang, P
creators_name: Chen, Y
title: The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G93
note: © 2021 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
abstract: 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.
date: 2021
date_type: published
official_url: https://doi.org/10.1038/s41419-021-03596-w
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1856565
doi: 10.1038/s41419-021-03596-w
pii: 10.1038/s41419-021-03596-w
lyricists_name: Ruan, Xiong-Zhong
lyricists_id: XZRUA13
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Cell Death & Disease
volume: 12
number: 4
article_number: 328
event_location: England
citation:        Luo, X;    Zheng, E;    Wei, L;    Zeng, H;    Qin, H;    Zhang, X;    Liao, M;                     ... Chen, Y; + view all <#>        Luo, X;  Zheng, E;  Wei, L;  Zeng, H;  Qin, H;  Zhang, X;  Liao, M;  Chen, L;  Zhao, L;  Ruan, XZ;  Yang, P;  Chen, Y;   - view fewer <#>    (2021)    The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis.                   Cell Death & Disease , 12  (4)    , Article 328.  10.1038/s41419-021-03596-w <https://doi.org/10.1038/s41419-021-03596-w>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10125859/1/s41419-021-03596-w.pdf