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Bayin NS, Frenster JD, Sen R, et al. Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells. Oncotarget. 2017;8(39):64932-64953doi: 10.18632/oncotarget.18117.
Bayin, N. S., Frenster, J. D., Sen, R., Si, S., Modrek, A. S., Galifianakis, N., Dolgalev, I., Ortenzi, V., Illa-Bochaca, I., Khahera, A., Serrano, J., Chiriboga, L., Zagzag, D., Golfinos, J. G., Doyle, W., Tsirigos, A., Heguy, A., Chesler, M., Barcellos-Hoff, M. H., Snuderl, M., & Placantonakis, D. G. (2017). Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells. Oncotarget, 8(39), 64932-64953. https://doi.org/10.18632/oncotarget.18117
Bayin, N Sumru, et al. "Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells." Oncotarget vol. 8,39 (2017): 64932-64953. doi: https://doi.org/10.18632/oncotarget.18117
Bayin NS, Frenster JD, Sen R, Si S, Modrek AS, Galifianakis N, Dolgalev I, Ortenzi V, Illa-Bochaca I, Khahera A, Serrano J, Chiriboga L, Zagzag D, Golfinos JG, Doyle W, Tsirigos A, Heguy A, Chesler M, Barcellos-Hoff MH, Snuderl M, Placantonakis DG. Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells. Oncotarget. 2017 May 23;8(39):64932-64953. doi: 10.18632/oncotarget.18117. eCollection 2017 Sep 12. PMID: 29029402; PMCID: PMC5630302.
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Oncotarget. 2017 May 23;8(39):64932-64953. doi: 10.18632/oncotarget.18117. eCollection 2017 Sep 12.

Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells.

Oncotarget

N Sumru Bayin, Joshua D Frenster, Rajeev Sen, Sheng Si, Aram S Modrek, Nataliya Galifianakis, Igor Dolgalev, Valerio Ortenzi, Irineu Illa-Bochaca, Anadjeet Khahera, Jonathan Serrano, Luis Chiriboga, David Zagzag, John G Golfinos, Werner Doyle, Aristotelis Tsirigos, Adriana Heguy, Mitch Chesler, Mary Helen Barcellos-Hoff, Matija Snuderl, Dimitris G Placantonakis

Affiliations

  1. Department of Neurosurgery, NYU School of Medicine, New York, NY, USA.
  2. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, USA.
  3. Developmental Biology Program, Sloan Kettering Institute, New York, NY, USA.
  4. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
  5. Neuroscience Institute, NYU School of Medicine, New York, NY, USA.
  6. Genome Technology Center, NYU School of Medicine, New York, NY, USA.
  7. Department of Pathology, NYU School of Medicine, New York, NY, USA.
  8. Department of Medicine, NYU School of Medicine, New York, NY, USA.
  9. Perlmutter Cancer Center, NYU School of Medicine, New York, NY, USA.
  10. Brain Tumor Center, NYU School of Medicine, New York, NY, USA.
  11. Applied Bioinformatics Laboratories, Office of Science & Research, NYU School of Medicine, New York, NY, USA.
  12. Department of Radiation Oncology, NYU School of Medicine, New York, NY, USA.
  13. Department of Radiation Oncology, University of California, San Francisco, CA, USA.

PMID: 29029402 PMCID: PMC5630302 DOI: 10.18632/oncotarget.18117

Abstract

Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch signaling, populate tumors regardless of local vascularity and selectively utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis and resistance to hypoxia. These findings demonstrate a novel role for Notch signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity ensures metabolic adaptations to support tumor growth in diverse tumor microenvironments.

Keywords: CD133; Notch signaling; glioblastoma stem cells; tumor metabolism; tumor vasculature

Conflict of interest statement

CONFLICTS OF INTEREST None

References

  1. N Engl J Med. 2014 Feb 20;370(8):699-708 - PubMed
  2. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  3. Nature. 2012 Aug 23;488(7412):522-6 - PubMed
  4. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):19059-64 - PubMed
  5. Cancer Cell. 2012 Oct 16;22(4):425-37 - PubMed
  6. Cell Rep. 2015 Jun 23;11(11):1809-21 - PubMed
  7. Cancer Cell. 2009 Jun 2;15(6):501-13 - PubMed
  8. Cell Cycle. 2009 Oct 15;8(20):3274-84 - PubMed
  9. Clin Cancer Res. 2016 Oct 1;22(19):4786-4796 - PubMed
  10. Cell Death Differ. 2011 May;18(5):829-40 - PubMed
  11. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3041-6 - PubMed
  12. Histopathology. 2012 Apr;60(5):740-7 - PubMed
  13. Cancer Res. 2011 Sep 15;71(18):6073-83 - PubMed
  14. Br J Cancer. 2010 Mar 2;102(5):789-95 - PubMed
  15. Biochem Pharmacol. 2010 Sep 1;80(5):654-65 - PubMed
  16. Cell. 2014 Apr 24;157(3):580-94 - PubMed
  17. Stem Cells. 2010 Jan;28(1):5-16 - PubMed
  18. Science. 2014 Jun 20;344(6190):1396-401 - PubMed
  19. Cancer Cell. 2006 Mar;9(3):157-73 - PubMed
  20. Bioinformatics. 2013 Jan 1;29(1):15-21 - PubMed
  21. Diabetes. 2008 Jun;57(6):1575-83 - PubMed
  22. Stem Cells. 2015 Jan;33(1):21-34 - PubMed
  23. N Engl J Med. 2014 Feb 20;370(8):709-22 - PubMed
  24. J Neurooncol. 2015 Jan;121(2):239-50 - PubMed
  25. Clin Cancer Res. 2010 Dec 15;16(24):6060-70 - PubMed
  26. J Neurooncol. 2008 Nov;90(2):157-70 - PubMed
  27. Nat Neurosci. 2013 Oct;16(10):1373-82 - PubMed
  28. Nature. 2007 Sep 20;449(7160):351-5 - PubMed
  29. Curr Opin Neurobiol. 2013 Dec;23(6):935-42 - PubMed
  30. Science. 2004 May 28;304(5675):1338-40 - PubMed
  31. J Exp Med. 2011 Feb 14;208(2):313-26 - PubMed
  32. PLoS One. 2014 Dec 26;9(12 ):e116114 - PubMed
  33. Mol Biol. 2006 May 1;40(3):396-405 - PubMed
  34. Cell Stem Cell. 2008 Sep 11;3(3):289-300 - PubMed
  35. Cancer Cell. 2006 May;9(5):391-403 - PubMed
  36. Cancer Res. 2007 Dec 1;67(23):11244-53 - PubMed
  37. Nat Rev Cancer. 2007 Oct;7(10 ):733-6 - PubMed
  38. Cell Metab. 2011 Dec 7;14 (6):768-79 - PubMed
  39. Stem Cells. 2010 Jan;28(1):17-28 - PubMed
  40. Cancer Cell. 2007 Jan;11(1):69-82 - PubMed
  41. J Neuropathol Exp Neurol. 2006 Jun;65(6):529-39 - PubMed
  42. Cancer Cell. 2011 Dec 13;20(6):810-7 - PubMed
  43. Stem Cells. 2010 Jun;28(6):1019-29 - PubMed
  44. Nature. 2010 Dec 9;468(7325):824-8 - PubMed
  45. Nature. 2004 Nov 18;432(7015):396-401 - PubMed
  46. Curr Top Microbiol Immunol. 2010;345:21-30 - PubMed
  47. Glia. 2001 Apr 15;34(2):143-9 - PubMed
  48. Cancer Cell. 2014 Nov 10;26(5):605-22 - PubMed
  49. Oncogenesis. 2016 Oct 24;5(10 ):e263 - PubMed
  50. Am J Pathol. 2010 Sep;177(3):1491-502 - PubMed
  51. Neoplasia. 2012 Feb;14 (2):150-8 - PubMed
  52. Clin Cancer Res. 2010 Dec 15;16(24):6049-59 - PubMed
  53. Stem Cells. 2009 Mar;27(3):521-32 - PubMed
  54. Brain. 2010 Apr;133(Pt 4):983-95 - PubMed
  55. Nature. 2006 Dec 7;444(7120):756-60 - PubMed
  56. Stem Cells. 2013 May;31(5):857-69 - PubMed
  57. Semin Radiat Oncol. 2009 Jul;19(3):163-70 - PubMed
  58. Nat Protoc. 2009;4(1):44-57 - PubMed
  59. PLoS One. 2015 Mar 03;10 (3):e0118201 - PubMed
  60. Oncogene. 2012 Jul 5;31(27):3235-43 - PubMed
  61. Front Oncol. 2013 Mar 07;3:38 - PubMed
  62. Cancer Res. 2011 Sep 15;71(18):6061-72 - PubMed
  63. Annu Rev Cell Biol. 1991;7:427-52 - PubMed
  64. Nat Commun. 2015 Apr 02;6:6411 - PubMed
  65. Cell. 2013 Mar 28;153(1):139-52 - PubMed
  66. Cancer Cell. 2010 Jan 19;17(1):98-110 - PubMed
  67. Radiother Oncol. 2007 Jun;83(3):398-405 - PubMed
  68. Nat Neurosci. 2005 Jun;8(6):709-15 - PubMed
  69. N Engl J Med. 2005 Mar 10;352(10 ):987-96 - PubMed
  70. Nat Protoc. 2015 Jan;10(1):53-74 - PubMed
  71. Nature. 2010 Dec 9;468(7325):829-33 - PubMed
  72. Genome Biol. 2014;15(12):550 - PubMed

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