Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
Nat Commun. 2019 Sep 4;10(1):3981. doi: 10.1038/s41467-019-11662-3.
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 Apc 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.
CD36 的多样化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 的表达水平从腺瘤到癌逐渐降低。CD36 的缺失预示着 CRC 患者预后不良。在 CRC 细胞中，CD36 作为一种肿瘤抑制因子，在体外和体内均能抑制有氧糖酵解。在机制上，CD36-Glypcian 4（GPC4）相互作用可以促进 GPC4 的蛋白酶体依赖泛素化，从而抑制β-catenin/c-myc 信号通路，并抑制下游糖酵解靶基因 GLUT1、HK2、PKM2 和 LDHA。此外，在炎症诱导的 CRC 模型以及 Apc 小鼠模型中破坏 CD36 显著增加了结直肠肿瘤的发生。我们的研究结果揭示了一个 CD36-GPC4-β-catenin-c-myc 信号轴，该信号轴调节 CRC 发展中的糖酵解，可能为 CRC 的预防提供一种干预策略。
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