HMGB1
2,6-二磷酸果糖
癌症研究
化疗
化学
医学
肿瘤科
内科学
生物化学
糖酵解
酶
炎症
磷酸果糖激酶
作者
Yeyi Li,Yuan Fu,Yan Zhang,Man Shang,Qiujing Yu,Ting Wang
出处
期刊:Social Science Research Network
[Social Science Electronic Publishing]
日期:2022-01-01
被引量:1
摘要
Metabolites may be the key to determining cell fate. Fructose-1,6-bisphosphate (F1,6P) is the rate-limiting product in glycolysis and the rate-limiting substrate in gluconeogenesis. Here, we discovered that the nuclear-accumulated F1,6P impairs cancer cell viability by directly binding to HMGB1, the most abundant non-histone chromosome structural protein with paradoxical roles in tumor development. F1,6P disrupts the association between the HMGB1 A-box and C-tail by targeting K43/K44 residues, inhibits HMGB1 oligomerization, and stabilizes P53 protein by increasing P53–HMGB1 interaction. Moreover, F1,6P lowers the affinity of HMGB1 for DNA and DNA adducts, which sensitizes cancer cells to chemotherapeutic drug(s)-induced DNA replication stress and DNA damage. Concordantly, F1,6P re-sensitizes cancer cells with chemotherapy resistance, impairs tumor growth and enhances chemosensitivity in mice, and impedes the growth of human tumor organoids. These findings reveal a novel role for nuclear-accumulated F1,6P and underscore the potential utility of F1,6P as a drug for cancer therapy.
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