糖酵解
磷酸果糖激酶
碳水化合物代谢
癌症研究
生物
细胞代谢
细胞生物学
化学
生物化学
新陈代谢
作者
Yingdan Huang,Xiong Chen,Chunmeng Wang,Jun Deng,Zhixiang Zuo,Huijing Wu,Jianping Xiong,Xiaohua Wu,Hua Lu,Qian Hao,Xiang Zhou
出处
期刊:Cell Reports
[Elsevier]
日期:2023-11-01
卷期号:42 (11): 113426-113426
被引量:2
标识
DOI:10.1016/j.celrep.2023.113426
摘要
Summary
Aerobic glycolysis is critical for cancer progression and can be exploited in cancer therapy. Here, we report that the human carboxymethylenebutenolidase homolog (carboxymethylenebutenolidase-like [CMBL]) acts as a tumor suppressor by reprogramming glycolysis in colorectal cancer (CRC). The anti-cancer action of CMBL is mediated through its interactions with the E3 ubiquitin ligase TRIM25 and the glycolytic enzyme phosphofructokinase-1 platelet type (PFKP). Ectopic CMBL enhances TRIM25 binding to PFKP, leading to the ubiquitination and proteasomal degradation of PFKP. Interestingly, CMBL is transcriptionally activated by p53 in response to genotoxic stress, and p53 activation represses glycolysis by promoting PFKP degradation. Remarkably, CMBL deficiency, which impairs p53's ability to inhibit glycolysis, makes tumors more sensitive to a combination therapy involving the glycolysis inhibitor 2-deoxyglucose. Taken together, our study demonstrates that CMBL suppresses CRC growth by inhibiting glycolysis and suggests a potential combination strategy for the treatment of CMBL-deficient CRC.
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