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Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells
Open accessAbstract
SUMMARY 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.
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Protein kinase C and other diacylglycerol effectors in cancer
Griner, E. M., & Kazanietz, M. G. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2110 · Cited by 978
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Self-citationEMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539
Self-citationGenome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth
Zanconato, F., Forcato, M., Battilana, G., Azzolin, L., Quaranta, E., Bodega, B., Rosato, A., Bicciato, S., Cordenonsi, M., & Piccolo, S. (2015) · Nature Cell Biology · doi:10.1038/ncb3216 · Cited by 1,219
The epigenetics of epithelial-mesenchymal plasticity in cancer
Tam, W. L., & Weinberg, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3336 · Cited by 1,163
Self-citationTackling the cancer stem cells — what challenges do they pose?
Pattabiraman, D. R., & Weinberg, R. A. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4253 · Cited by 990
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Metadata
- Authors
- Tam, W. L., Lu, H., Buikhuisen, J., Soh, B. S., Lim, E., Reinhardt, F., Wu, Z. J., Krall, J. A., Bierie, B., Guo, W., Chen, X., Liu, X. S., Brown, M., Lim, B., & Weinberg, R. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 24
- Issue
- 3
- Pages
- 347-364
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2086596704
- Cited by
- 321
- References
- 1
- FWCI
- 15.02
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Tam, W. L., Lu, H., Buikhuisen, J., Soh, B. S., Lim, E., Reinhardt, F., Wu, Z. J., Krall, J. A., Bierie, B., Guo, W., Chen, X., Liu, X. S., Brown, M., Lim, B., & Weinberg, R. A. (2013). Protein Kinase C α Is a Central Signaling Node and Therapeutic Target for Breast Cancer Stem Cells. Cancer Cell. https://doi.org/10.1016/j.ccr.2013.08.005
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