Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2

作     者：Mingyue Tan Qi Pan Qi Wu Jianfa Li Jun Wang Mingyue Tan;Qi Pan;Qi Wu;Jianfa Li;Jun Wang

作者机构：Department of UrologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Urology CenterShuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Department of UrologyThe Sixth Affiliated Hospital of Wenzhou Medical University(The People’s Hospital of Lishui)Lishui 323000China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2023年第17卷第3期

页      面：503-517页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：financially supported by grants from the National Natural Science Foundation of China(Nos.82002683 and 81902569). 

主　　题：ALDOB kidney cancer cell proliferation 

摘      要：Aldolase B(ALDOB),a glycolytic enzyme,is uniformly depleted in clear cell renal cell carcinoma(ccRCC)tissues.We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC,but the mechanism was not unequivocally identified.We showed that the corepressor C-terminal-binding protein 2(CtBP2)is a novel ALDOB-interacting protein in ccRCC.The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival.ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor,proapoptotic,and epithelial marker genes.Furthermore,ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner.Mechanistically,our findings showed that ALDOB recruited acireductone dioxygenase 1,which catalyzes the synthesis of an endogenous inhibitor of CtBP2,4-methylthio 2-oxobutyric acid.ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2,and this scaffolding effect was independent of ALDOB enzymatic activity.Moreover,increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo.Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.