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

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

机构地区：[1]Department of Urology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [2]Urology Center,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [3]Department of Urology,The Sixth Affiliated Hospital of Wenzhou Medical University(The People’s Hospital of Lishui),Lishui 323000,China

出　　处：《Frontiers of Medicine》2023年第3期503-517,共15页医学前沿（英文版）

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

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.

关 键 词：ALDOB kidney cancer cell proliferation 

分 类 号：R737.11[医药卫生—肿瘤]