USP1 inhibition suppresses the progression of osteosarcoma via destabilizing TAZ.
Int J Biol Sci
; 18(8): 3122-3136, 2022.
Article
em En
| MEDLINE
| ID: mdl-35637948
ABSTRACT
Mutations and altered expression of deubiquitinating enzymes (DUBs) profoundly influence tumor progression. Ubiquitin-specific protease 1 (USP1) is a well-characterized human DUB reportedly overexpressed in and associated with maintaining the mesenchymal stem cell status of osteosarcoma (OS); however, the potential mechanisms of USP1 in OS remain poorly understood. In this study, we identified that USP1 directly interacts with Transcriptional Co-Activator With PDZ-Binding Motif (TAZ) in OS cell lines, and with mechanistic analysis indicating that the anti-OS effects of USP1 inhibition could be partially attributed to TAZ instability, with its reduced nuclear accumulation responsible for a subsequent decrease in the expression of downstream genes associated with the Hippo signaling pathway. Moreover, pharmacological inhibition USP1 by ML323 presented the similar effects on Hippo signaling pathway and suppressed OS growth and metastasis both in vitro and in vivo. Taken together, our results revealed a novel molecular mechanism underlying the function of USP1 in OS and a potential role of ML323 as a therapeutic strategy for the clinical treatment of OS.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
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Osteossarcoma
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Proteases Específicas de Ubiquitina
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Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article