CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis

Yuan Fang, Zhi-Yong Shen, Yi-Zhi Zhan, Xiao-Chuang Feng, Ke-Li Chen, Yong-Sheng Li, Hai-Jun Deng, Su-Ming Pan, Wu De-Hua () and Yi Ding ()
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Yuan Fang: Southern Medical University
Zhi-Yong Shen: Southern Medical University
Yi-Zhi Zhan: Southern Medical University
Xiao-Chuang Feng: Southern Medical University
Ke-Li Chen: Southern Medical University
Yong-Sheng Li: Southern Medical University
Hai-Jun Deng: Southern Medical University
Su-Ming Pan: Yue Bei People’s Hospital
Wu De-Hua: Southern Medical University
Yi Ding: Southern Medical University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of β-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as ApcMin/+ mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-β-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.

Date: 2019
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DOI: 10.1038/s41467-019-11662-3

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