Phosphorylation-independent mTORC1 inhibition by the autophagy inducer Rottlerin.
Cancer Lett
; 360(1): 17-27, 2015 Apr 28.
Article
en En
| MEDLINE
| ID: mdl-25661734
ABSTRACT
We recently found that Rottlerin not only inhibits proliferation but also causes Bcl-2- and Beclin 1-independent autophagic death in apoptosis-resistant breast adenocarcinoma MCF-7 cells. Having excluded a role for canonical signaling pathways, the current study was aimed to investigate the contribution of the AMPK/mTOR axis in autophagy induction and to search for the upstream signaling molecules potentially targeted by Rottlerin. Using several enzyme inhibitors, Western blotting analysis, mTOR siRNA and pull down assay, we demonstrate that the Rottlerin-triggered autophagy is mediated by inhibition of mTORC1 activity through a novel AMPK and mTORC1 phosphorylation-independent mechanism, likely mediated by the direct interaction between Rottlerin and mTOR.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acetofenonas
/
Autofagia
/
Benzopiranos
/
Neoplasias de la Mama
/
Adenocarcinoma
/
Complejos Multiproteicos
/
Inhibidores de Proteínas Quinasas
/
Serina-Treonina Quinasas TOR
/
Antineoplásicos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
IE
/
IRELAND
/
IRLANDA