AMPK ß1 reduces tumor progression and improves survival in p53 null mice.
Mol Oncol
; 11(9): 1143-1155, 2017 09.
Article
en En
| MEDLINE
| ID: mdl-28544264
ABSTRACT
The AMP-activated protein kinase (AMPK) is a heterotrimeric protein complex that is an important sensor of cellular energy status. Reduced expression of the AMPK ß1 isoform has been linked to reduced survival in different cancers, but whether this accelerates tumor progression and the potential mechanism mediating these effects are not known. Furthermore, it is unknown whether AMPK ß1 is implicated in tumorigenesis, and if so, what tissues may be most sensitive. In the current study, we find that in the absence of the tumor suppressor p53, germline genetic deletion of AMPK ß1 accelerates the appearance of a T-cell lymphoma that reduces lifespan compared to p53 deficiency alone. This increased tumorigenesis is linked to increases in interleukin-1ß (IL1ß), reductions in acetyl-CoA carboxylase (ACC) phosphorylation, and elevated lipogenesis. Collectively, these data indicate that reductions in the AMPK ß1 subunit accelerate the development of T-cell lymphoma, suggesting that therapies targeting this AMPK subunit or inhibiting lipogenesis may be effective for limiting the proliferation of p53-mutant tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfoma de Células T
/
Proteína p53 Supresora de Tumor
/
Progresión de la Enfermedad
/
Proteínas Quinasas Activadas por AMP
Límite:
Animals
Idioma:
En
Revista:
Mol Oncol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2017
Tipo del documento:
Article
País de afiliación:
Canadá