The actin-bundling protein palladin is an Akt1-specific substrate that regulates breast cancer cell migration.
Mol Cell
; 38(3): 333-44, 2010 May 14.
Article
em En
| MEDLINE
| ID: mdl-20471940
ABSTRACT
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is frequently deregulated in cancer. Downstream of PI3K, Akt1 and Akt2 have opposing roles in breast cancer invasive migration, leading to metastatic dissemination. Here, we identify palladin, an actin-associated protein, as an Akt1-specific substrate that modulates breast cancer cell invasive migration. Akt1, but not Akt2, phosphorylates palladin at Ser507 in a domain that is critical for F-actin bundling. Downregulation of palladin enhances migration and invasion of breast cancer cells and induces abnormal branching morphogenesis in 3D cultures. Palladin phosphorylation at Ser507 is required for Akt1-mediated inhibition of breast cancer cell migration and also for F-actin bundling, leading to the maintenance of an organized actin cytoskeleton. These findings identify palladin as an Akt1-specific substrate that regulates cell motility and provide a molecular mechanism that accounts for the functional distinction between Akt isoforms in breast cancer cell signaling to cell migration.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Citoesqueleto
/
Neoplasias da Mama
/
Movimento Celular
/
Actinas
/
Proteínas do Citoesqueleto
/
Proteínas Proto-Oncogênicas c-akt
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Mol Cell
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos