Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2 / 医学前沿
Frontiers of Medicine
; (4): 503-517, 2023.
Article
在 En
| WPRIM
| ID: wpr-982571
Responsible library:
WPRO
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.
Key words
全文:
1
索引:
WPRIM
主要主题:
Transcription Factors
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Carcinoma, Renal Cell
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Gene Expression Regulation, Neoplastic
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Cell Line, Tumor
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Cell Proliferation
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Co-Repressor Proteins
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Fructose-Bisphosphate Aldolase
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Kidney Neoplasms
限制:
Humans
语言:
En
期刊:
Frontiers of Medicine
年:
2023
类型:
Article