CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis
CD36 inhibits β-catenin/c-myc-mediated glycolysis through ubiquitination of GPC4 to repress colorectal tumorigenesis
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CD36 通过 GPC4 泛素化抑制 β-catenin/c-myc 介导的糖酵解，从而抑制结直肠肿瘤发生
DOI：
10.1038/s41467-019-11662-3
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发表时间：
2019-09-04
影响因子：
16.6
通讯作者：
Ding, Yi
中科院分区：
文献类型：
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作者：
Fang, Yuan;Shen, Zhi-Yong;Ding, Yi
CD36的多种表达模式反映了其多种细胞功能。然而，CD36在结直肠癌（CRC）中的作用尚不清楚。在这里，我们发现CD36的表达从腺瘤到癌逐渐减少。CD36缺失预示着结直肠癌患者的不良生存率。在CRC细胞中，CD36作为肿瘤抑制因子，在体外和体内抑制有氧糖酵解。机制上，CD36-Glypcian 4 （GPC4）相互作用可促进蛋白酶体依赖的GPC4泛素化，随后抑制β -catenin/c-myc信号传导，抑制下游糖酵解靶基因GLUT1、HK2、PKM2和LDHA。此外，在炎症诱导的CRC模型和Apc（Min/+）小鼠模型中，CD36的破坏显著增加了结直肠肿瘤的发生。我们的研究结果揭示了cd36 - gpc4 - β -catenin-c-myc信号轴在CRC发展过程中调节糖酵解，并可能为CRC预防提供干预策略。
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 beta-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 Apc(Min/+) mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-beta-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.