Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2.
10.1007/s11684-022-0947-9
- Author:
Mingyue TAN
1
;
Qi PAN
1
;
Qi WU
1
;
Jianfa LI
1
;
Jun WANG
2
Author Information
1. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
2. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. linkwj@shsmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
ALDOB;
cell proliferation;
kidney cancer
- MeSH:
Humans;
Carcinoma, Renal Cell/genetics*;
Fructose-Bisphosphate Aldolase/metabolism*;
Co-Repressor Proteins/metabolism*;
Transcription Factors/genetics*;
Kidney Neoplasms/genetics*;
Cell Line, Tumor;
Cell Proliferation/genetics*;
Gene Expression Regulation, Neoplastic
- From:
Frontiers of Medicine
2023;17(3):503-517
- CountryChina
- Language:English
-
Abstract:
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.
