Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells
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nihms569426.pdf
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2.3 MB
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Author(s)
Lu, Haihui
Buikhuisen, Joyce
Soh, Boon Seng
Lim, Elgene
Reinhardt, Ferenc
Wu, Zhenhua Jeremy
Krall, Jordan A.
Bierie, Brian
Guo, Wenjun
Chen, Xi
Date Issued
September 2013
Journal
Cancer Cell
Publisher
Elsevier
Citation
Tam, Wai Leong et al. “Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells.” Cancer Cell 24, 3 (September 2013): 347–364 © 2013 Elsevier Inc
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CCR.2013.08.005
