Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.
Cancer Cell
; 24(3): 347-64, 2013 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-24029232
ABSTRACT
The epithelial-mesenchymal transition program becomes activated during malignant progression and can enrich for cancer stem cells (CSCs). We report that inhibition of protein kinase C α (PKCα) specifically targets CSCs but has little effect on non-CSCs. The formation of CSCs from non-stem cells involves a shift from EGFR to PDGFR signaling and results in the PKCα-dependent activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCα and FRA1 expression is associated with the aggressive triple-negative breast cancers, and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence, identifying molecular features that shift between cell states can be exploited to target signaling components critical to CSCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Neoplasias da Mama
/
Transdução de Sinais
/
Proteína Quinase C-alfa
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos