Ahnak functions as a tumor suppressor via modulation of TGFß/Smad signaling pathway.
Oncogene
; 33(38): 4675-84, 2014 Sep 18.
Article
en En
| MEDLINE
| ID: mdl-24662814
ABSTRACT
We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Smad
/
Proteínas de la Membrana
/
Proteínas de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Oncogene
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2014
Tipo del documento:
Article