The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
c-Myc Is Required for Maintenance of Glioma Cancer Stem Cells
Open accessAbstract
BACKGROUND: Malignant gliomas rank among the most lethal cancers. Gliomas display a striking cellular heterogeneity with a hierarchy of differentiation states. Recent studies support the existence of cancer stem cells in gliomas that are functionally defined by their capacity for extensive self-renewal and formation of secondary tumors that phenocopy the original tumors. As the c-Myc oncoprotein has recognized roles in normal stem cell biology, we hypothesized that c-Myc may contribute to cancer stem cell biology as these cells share characteristics with normal stem cells. METHODOLOGY/PRINCIPAL FINDINGS: Based on previous methods that we and others have employed, tumor cell populations were enriched or depleted for cancer stem cells using the stem cell marker CD133 (Prominin-1). We characterized c-Myc expression in matched tumor cell populations using real time PCR, immunoblotting, immunofluorescence and flow cytometry. Here we report that c-Myc is highly expressed in glioma cancer stem cells relative to non-stem glioma cells. To interrogate the significance of c-Myc expression in glioma cancer stem cells, we targeted its expression using lentivirally transduced short hairpin RNA (shRNA). Knockdown of c-Myc in glioma cancer stem cells reduced proliferation with concomitant cell cycle arrest in the G(0)/G(1) phase and increased apoptosis. Non-stem glioma cells displayed limited dependence on c-Myc expression for survival and proliferation. Further, glioma cancer stem cells with decreased c-Myc levels failed to form neurospheres in vitro or tumors when xenotransplanted into the brains of immunocompromised mice. CONCLUSIONS/SIGNIFICANCE: These findings support a central role of c-Myc in regulating proliferation and survival of glioma cancer stem cells. Targeting core stem cell pathways may offer improved therapeutic approaches for advanced cancers.
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Cites
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A cell initiating human acute myeloid leukaemia after transplantation into SCID mice
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MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer
Shachaf, C. M., Kopelman, A. M., Arvanitis, C., Karlsson, Å., Beer, S., Mandl, S., Bachmann, M. H., Borowsky, A. D., Ruebner, B., Cardiff, R. D., et al. (2004) · Nature · doi:10.1038/nature03043 · Cited by 874
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
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THE MANY ROLES OF c-Myc IN APOPTOSIS
Thompson, E. B. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.575 · Cited by 328 · cited 1×
“Previous reports have demonstrated that c-Myc promotes apoptosis in cancer cell lines and various normal cell types, whereas downregulation of c-Myc also leads to apoptosis under certain circumstances [30,31,32,33].”
BackgroundDeregulated expression of c-Myc depletes epidermal stem cells
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Cited by
Cancer stem cells in glioblastoma
Lathia, J. D., Mack, S. C., Mulkearns-Hubert, E. E., Valentim, C. L. L., & Rich, J. N. (2015) · Genes & Development · doi:10.1101/gad.261982.115 · Cited by 1,520
Self-citationHeddleston, J. M., Li, Z., McLendon, R. E., Hjelmeland, A. B., & Rich, J. N. (2009) · Cell Cycle · doi:10.4161/cc.8.20.9701 · Cited by 813
Self-citationInhibition of BET Bromodomain Targets Genetically Diverse Glioblastoma
Cheng, Z., Gong, Y., Ma, Y., Lu, K., Lu, X., Pierce, L. A., Thompson, R. C., Muller, S., Knapp, S., & Wang, J. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-3066 · Cited by 299
Self-citationCancer Stem Cell Hierarchy in Glioblastoma Multiforme
Bradshaw, A., Wickremsekera, A., Tan, S. T., Peng, L., Davis, P. F., & Itinteang, T. (2016) · Frontiers in Surgery · doi:10.3389/fsurg.2016.00021 · Cited by 258
Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting
Huang, Z., Cheng, L., Guryanova, O. A., Wu, Q., & Bao, S. (2010) · Protein & Cell · doi:10.1007/s13238-010-0078-y · Cited by 248
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Metadata
- Authors
- Wang, J., Wang, H., Li, Z., Wu, Q., Lathia, J. D., McLendon, R. E., Hjelmeland, A. B., & Rich, J. N.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-11-20
- Volume
- 3
- Issue
- 11
- Pages
- e3769
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2031182614
- Cited by
- 429
- References
- 7
- FWCI
- 9.70
- Type
- journal article
- Language
- en
- Open access
- gold
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