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The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer
Open accessAbstract
BACKGROUND: Pancreatic cancer stem cells (CSCs) represent a small subpopulation of pancreatic cancer cells that have the capacity to initiate and propagate tumor formation. However, the mechanisms by which pancreatic CSCs are maintained are not well understood or characterized. METHODS: Expression of Notch receptors, ligands, and Notch signaling target genes was quantitated in the CSC and non-CSC populations from 8 primary human pancreatic xenografts. A gamma secretase inhibitor (GSI) that inhibits the Notch pathway and a shRNA targeting the Notch target gene Hes1 were used to assess the role of the Notch pathway in CSC population maintenance and pancreatic tumor growth. RESULTS: Notch pathway components were found to be upregulated in pancreatic CSCs. Inhibition of the Notch pathway using either a gamma secretase inhibitor or Hes1 shRNA in pancreatic cancer cells reduced the percentage of CSCs and tumorsphere formation. Conversely, activation of the Notch pathway with an exogenous Notch peptide ligand increased the percentage of CSCs as well as tumorsphere formation. In vivo treatment of orthotopic pancreatic tumors in NOD/SCID mice with GSI blocked tumor growth and reduced the CSC population. CONCLUSION: The Notch signaling pathway is important in maintaining the pancreatic CSC population and is a potential therapeutic target in pancreatic cancer.
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Cites
Notch mediates TGFα-induced changes in epithelial differentiation during pancreatic tumorigenesis
Miyamoto, Y., Maitra, A., Ghosh, B., Zechner, U., Argani, P., Iacobuzio-Donahue, C. A., Sriuranpong, V., Iso, T., Meszoely, I. M., Wolfe, M. S., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00140-5 · Cited by 643
Metadata
- Authors
- Abel, E. V., Kim, E. J., Wu, J., Hynes, M., Bednar, F., Proctor, E., Wang, L., Dziubinski, M. L., & Simeone, D. M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-03-19
- Volume
- 9
- Issue
- 3
- Pages
- e91983
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2057881265
- Cited by
- 169
- References
- 1
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer. https://app.cochat.ai/papers/10.1371/journal.pone.0091983
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- Abel, E. V., Kim, E. J., Wu, J., Hynes, M., Bednar, F., Proctor, E., Wang, L., Dziubinski, M. L., & Simeone, D. M. (2014). The Notch Pathway Is Important in Maintaining the Cancer Stem Cell Population in Pancreatic Cancer. PLoS ONE. https://doi.org/10.1371/journal.pone.0091983
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