The DOI matches its Crossref record; 79 of the 79 references it cites were found in a registry or an index.
Notch Promotes Radioresistance of Glioma Stem Cells
Open accessAbstract
Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radioresistance in gliomas and breast cancers. The Notch pathway is critically implicated in stem cell fate determination and cancer. In this study, we show that inhibition of Notch pathway with γ-secretase inhibitors (GSIs) renders the glioma stem cells more sensitive to radiation at clinically relevant doses. GSIs enhance radiation-induced cell death and impair clonogenic survival of glioma stem cells but not non-stem glioma cells. Expression of the constitutively active intracellular domains of Notch1 or Notch2 protect glioma stem cells against radiation. Notch inhibition with GSIs does not alter the DNA damage response of glioma stem cells after radiation but rather reduces Akt activity and Mcl-1 levels. Finally, knockdown of Notch1 or Notch2 sensitizes glioma stem cells to radiation and impairs xenograft tumor formation. Taken together, our results suggest a critical role of Notch signaling to regulate radioresistance of glioma stem cells. Inhibition of Notch signaling holds promise to improve the efficiency of current radiotherapy in glioma treatment.
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Cites
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Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
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Self-citationThe BCL-2 protein family: opposing activities that mediate cell death
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Cited by
Targeting cancer stem cell pathways for cancer therapy
Yang, L., Shi, P., Zhao, G., Xu, J., Peng, W., Zhang, J., Zhang, G., Wang, X., Dong, Z., Chen, F., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0110-5 · Cited by 1,906
Self-citationCancer stem cells in glioblastoma
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Self-citationMolecular mechanisms of tumor resistance to radiotherapy
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Glioblastoma Stem Cells: Driving Resilience through Chaos
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Metadata
- Authors
- Wang, J., Wakeman, T. P., Lathia, J. D., Hjelmeland, A. B., Wang, X.-F., White, R. R., Rich, J. N., & Sullenger, B. A.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-11-17
- Volume
- 28
- Issue
- 1
- Pages
- 17-28
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2106675906
- Cited by
- 656
- References
- 79
- FWCI
- 20.54
- Type
- journal article
- Language
- en
- Open access
- green
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