PTBP1-Mediated Alternative Splicing Regulates the Inflammatory Secretome and the Pro-tumorigenic Effects of Senescent Cells.
Cancer Cell
; 34(1): 85-102.e9, 2018 07 09.
Article
en En
| MEDLINE
| ID: mdl-29990503
ABSTRACT
Oncogene-induced senescence is a potent tumor-suppressive response. Paradoxically, senescence also induces an inflammatory secretome that promotes carcinogenesis and age-related pathologies. Consequently, the senescence-associated secretory phenotype (SASP) is a potential therapeutic target. Here, we describe an RNAi screen for SASP regulators. We identified 50 druggable targets whose knockdown suppresses the inflammatory secretome and differentially affects other SASP components. Among the screen candidates was PTBP1. PTBP1 regulates the alternative splicing of genes involved in intracellular trafficking, such as EXOC7, to control the SASP. Inhibition of PTBP1 prevents the pro-tumorigenic effects of the SASP and impairs immune surveillance without increasing the risk of tumorigenesis. In conclusion, our study identifies SASP inhibition as a powerful and safe therapy against inflammation-driven cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
/
Senescencia Celular
/
Proteína de Unión al Tracto de Polipirimidina
/
Ribonucleoproteínas Nucleares Heterogéneas
/
Inflamación
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Cell
Asunto de la revista:
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido