Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2 / 医学前沿
Frontiers of Medicine
; (4): 503-517, 2023.
Article
em En
| WPRIM
| ID: wpr-982571
Biblioteca responsável:
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.
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Texto completo:
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Índice:
WPRIM
Assunto principal:
Fatores de Transcrição
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Carcinoma de Células Renais
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Regulação Neoplásica da Expressão Gênica
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Linhagem Celular Tumoral
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Proliferação de Células
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Proteínas Correpressoras
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Frutose-Bifosfato Aldolase
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Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
Frontiers of Medicine
Ano de publicação:
2023
Tipo de documento:
Article