PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer.
Cancer Res
; 77(17): 4613-4625, 2017 09 01.
Article
em En
| MEDLINE
| ID: mdl-28655788
ABSTRACT
Through an shRNA screen, we identified the protein arginine methyltransferase Prmt1 as a vulnerable intervention point in murine p53/Rb-null osteosarcomas, the human counterpart of which lacks effective therapeutic options. Depletion of Prmt1 in p53-deficient cells impaired tumor initiation and maintenance in vitro and in vivo Mechanistic studies reveal that translation-associated pathways were enriched for Prmt1 downstream targets, implicating Prmt1 in translation control. In particular, loss of Prmt1 led to a decrease in arginine methylation of the translation initiation complex, thereby disrupting its assembly and inhibiting translation. p53/Rb-null cells were sensitive to p53-induced translation stress, and analysis of human cancer cell line data from Project Achilles further revealed that Prmt1 and translation-associated pathways converged on the same functional networks. We propose that targeted therapy against Prmt1 and its associated translation-related pathways offer a mechanistic rationale for treatment of osteosarcomas and other cancers that exhibit dependencies on translation stress response. Cancer Res; 77(17); 4613-25. ©2017 AACR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína-Arginina N-Metiltransferases
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Biossíntese de Proteínas
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Neoplasias Ósseas
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Osteossarcoma
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Proteína Supressora de Tumor p53
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Proteína do Retinoblastoma
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2017
Tipo de documento:
Article