ARF and p53 coordinate tumor suppression of an oncogenic IFN-ß-STAT1-ISG15 signaling axis.
Cell Rep
; 7(2): 514-526, 2014 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-24726362
ABSTRACT
The ARF and p53 tumor suppressors are thought to act in a linear pathway to prevent cellular transformation in response to various oncogenic signals. Here, we show that loss of p53 leads to an increase in ARF protein levels, which function to limit the proliferation and tumorigenicity of p53-deficient cells by inhibiting an IFN-ß-STAT1-ISG15 signaling axis. Human triple-negative breast cancer (TNBC) tumor samples with coinactivation of p53 and ARF exhibit high expression of both STAT1 and ISG15, and TNBC cell lines are sensitive to STAT1 depletion. We propose that loss of p53 function and subsequent ARF induction creates a selective pressure to inactivate ARF and propose that tumors harboring coinactivation of ARF and p53 would benefit from therapies targeted against STAT1 and ISG15 activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Ubiquitinas
/
Citocinas
/
Proteína Supressora de Tumor p53
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Interferon beta
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Fatores de Ribosilação do ADP
Limite:
Animals
/
Female
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos