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Cancer Cell. 2013 Sep 9;24(3):347-64. doi: 10.1016/j.ccr.2013.08.005.

Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.

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1
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; MIT Ludwig Center for Molecular Oncology, Cambridge, MA 02139, USA.

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.

PMID:
24029232
PMCID:
PMC4001722
DOI:
10.1016/j.ccr.2013.08.005
[Indexed for MEDLINE]
Free PMC Article

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