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Masliantsev K, Pinel B, Balbous A, et al. Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome. Oncotarget. 2017;9(3):3968-3979doi: 10.18632/oncotarget.23374.
Masliantsev, K., Pinel, B., Balbous, A., Guichet, P. O., Tachon, G., Milin, S., Godet, J., Duchesne, M., Berger, A., Petropoulos, C., Wager, M., & Karayan-Tapon, L. (2018). Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome. Oncotarget, 9(3), 3968-3979. https://doi.org/10.18632/oncotarget.23374
Masliantsev, Konstantin, et al. "Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome." Oncotarget vol. 9,3 (2018): 3968-3979. doi: https://doi.org/10.18632/oncotarget.23374
Masliantsev K, Pinel B, Balbous A, Guichet PO, Tachon G, Milin S, Godet J, Duchesne M, Berger A, Petropoulos C, Wager M, Karayan-Tapon L. Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome. Oncotarget. 2017 Dec 16;9(3):3968-3979. doi: 10.18632/oncotarget.23374. eCollection 2018 Jan 09. PMID: 29423098; PMCID: PMC5790515.
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Oncotarget. 2017 Dec 16;9(3):3968-3979. doi: 10.18632/oncotarget.23374. eCollection 2018 Jan 09.

Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome.

Oncotarget

Konstantin Masliantsev, Baptiste Pinel, Anaïs Balbous, Pierre-Olivier Guichet, Gaëlle Tachon, Serge Milin, Julie Godet, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Michel Wager, Lucie Karayan-Tapon

Affiliations

  1. Inserm U1084, Laboratoire de Neurosciences Expérimentales et Cliniques, Poitiers F-86073, France.
  2. Université de Poitiers, Poitiers F-86073, France.
  3. CHU de Poitiers, Laboratoire de Cancérologie Biologique, Poitiers F-86022, France.
  4. CHU de Poitiers, Service d'Oncologie Radiothérapique, Poitiers F-86021, France.
  5. CHU de Poitiers, Service d'Anatomo-Cytopathologie, Poitiers F-86021, France.
  6. CHU de Poitiers, Service de Neurochirurgie, Poitiers F-86021, France.

PMID: 29423098 PMCID: PMC5790515 DOI: 10.18632/oncotarget.23374

Abstract

Glioblastoma (GBM) represents the most common and lethal primary malignant brain tumor. The standard treatment for glioblastoma patients involves surgical resection with concomitant radio and chemotherapy. Despite today's clinical protocol, the prognosis for patients remains very poor with a median survival of 15 months. Tumor resistance and recurrence is strongly correlated with a subpopulation of highly radioresistant and invasive cells termed Glioblastoma Stem Cells (GSCs). The transcription factor STAT3 has been found to be constitutively activated in different tumors including GBM and enhanced tumor radioresistance. In this study, we assessed radiosensitization of GSC lines isolated from patients by inhibition of STAT3 activation using Stattic or WP1066. We showed that inhibitor treatment before cell irradiation decreased the surviving fraction of GSCs suggesting that STAT3 inhibition could potentiate radiation effects. Finally, we investigated STAT3 activation status on 61 GBM clinical samples and found a preferential phosphorylation of STAT3 on Serine727 (pS727). Moreover, we found that pS727 was associated with a significant lower overall patient survival and progression-free survival but not pY705. Taken together, our results suggest that pS727-STAT3 could be a potential prognostic marker and could constitute a therapeutic target to sensitize highly radioresistant GSCs.

Keywords: Stat3; cancer stem cells; glioblastoma; radioresistance; static

Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts to disclose.

References

  1. Cancer Res. 2014 Sep 15;74(18):5218-28 - PubMed
  2. Mol Cancer Ther. 2012 Sep;11(9):1863-72 - PubMed
  3. Science. 1994 Jan 7;263(5143):89-92 - PubMed
  4. J Biol Chem. 1999 Aug 20;274(34):24392-400 - PubMed
  5. Mol Cancer Ther. 2014 Sep;13(9):2159-69 - PubMed
  6. Mol Med Rep. 2013 Jun;7(6):1883-8 - PubMed
  7. Dev Genet. 1996;19(2):139-45 - PubMed
  8. Curr Biol. 2000 Jan 13;10(1):47-50 - PubMed
  9. Oncogene. 2004 Dec 16;23(58):9392-400 - PubMed
  10. Int J Cancer. 2011 Feb 15;128(4):826-38 - PubMed
  11. Am J Pathol. 2012 May;180(5):2108-19 - PubMed
  12. Neuro Oncol. 2014 Jul;16(7):896-913 - PubMed
  13. Cancer Cell. 2006 Mar;9(3):157-73 - PubMed
  14. Int J Clin Exp Pathol. 2014 May 15;7(6):3141-9 - PubMed
  15. Mol Oncol. 2015 Jun;9(6):1194-206 - PubMed
  16. Cancer Res. 2002 Nov 15;62(22):6659-66 - PubMed
  17. PLoS One. 2013;8(1):e54565 - PubMed
  18. Int J Exp Pathol. 2010 Dec;91(6):506-14 - PubMed
  19. Cell Growth Differ. 1997 Dec;8(12):1267-76 - PubMed
  20. Immunity. 1996 Nov;5(5):449-60 - PubMed
  21. J Immunol. 1997 May 1;158(9):4097-103 - PubMed
  22. Cancer Res Treat. 2015 Oct;47(4):607-15 - PubMed
  23. Neuro Oncol. 2013 Feb;15(2):198-207 - PubMed
  24. Cell. 1995 Jul 28;82(2):241-50 - PubMed
  25. Curr Cancer Drug Targets. 2007 Jun;7(4):335-42 - PubMed
  26. Cancer Cell. 2013 Jun 10;23 (6):839-52 - PubMed
  27. Med Oncol. 2014 Apr;31(4):924 - PubMed
  28. Radiother Oncol. 2007 Jun;83(3):289-95 - PubMed
  29. Brain Pathol. 2016 Jan;26(1):18-30 - PubMed
  30. Stem Cells. 2010 Jan;28(1):17-28 - PubMed
  31. Cancer Cell. 2011 Apr 12;19(4):498-511 - PubMed
  32. Nat Rev Cancer. 2004 Feb;4(2):97-105 - PubMed
  33. Genes Dev. 2008 Feb 15;22(4):436-48 - PubMed
  34. J Neurosurg. 2017 Jan;126(1):249-259 - PubMed
  35. Cell Div. 2010 May 17;5:14 - PubMed
  36. Int J Cancer. 2014 Feb 15;134(4):997-1007 - PubMed
  37. Cancer Res. 2003 Sep 15;63(18):5821-8 - PubMed
  38. Int J Cancer. 2005 Jun 10;115(2):202-13 - PubMed
  39. Mol Cancer Ther. 2006 Nov;5(11):2659-65 - PubMed
  40. Chem Biol. 2006 Nov;13(11):1235-42 - PubMed
  41. Int J Radiat Oncol Biol Phys. 2010 Jul 15;77(4):1223-31 - PubMed
  42. Cancer Res. 2004 Oct 1;64(19):7011-21 - PubMed
  43. Oncotarget. 2014 Sep 30;5(18):8416-28 - PubMed
  44. Am J Pathol. 2005 Oct;167(4):969-80 - PubMed
  45. Mol Cell Biol. 1996 Apr;16(4):1595-603 - PubMed
  46. Cancer Res. 2007 Oct 15;67(20):9630-6 - PubMed
  47. Oncogene. 2002 Dec 5;21(55):8404-13 - PubMed
  48. Mol Cancer Res. 2008 May;6(5):675-84 - PubMed
  49. Int J Oncol. 2013 Jul;43(1):219-27 - PubMed
  50. Nature. 2006 Dec 7;444(7120):756-60 - PubMed
  51. Radiat Res. 2017 Mar;187(3):382-396 - PubMed
  52. Oral Oncol. 2012 Dec;48(12):1220-6 - PubMed
  53. Stem Cells. 2009 Oct;27(10):2383-92 - PubMed
  54. Cancer Sci. 2010 Jun;101(6):1417-23 - PubMed
  55. BMC Cancer. 2016 Aug 05;16:604 - PubMed
  56. PLoS One. 2013 Dec 30;8(12):e83971 - PubMed
  57. Int J Gynecol Cancer. 2013 May;23(4):608-14 - PubMed
  58. Cell. 1994 Apr 8;77(1):63-71 - PubMed
  59. Nature. 2010 Jan 21;463(7279):318-25 - PubMed
  60. Cancer Cell. 2010 Jan 19;17(1):98-110 - PubMed
  61. Oncogenesis. 2014 Mar 17;3:e91 - PubMed
  62. Science. 1995 Jul 7;269(5220):81-3 - PubMed
  63. Exp Hematol. 2003 May;31(5):398-405 - PubMed
  64. N Engl J Med. 2005 Mar 10;352(10 ):987-96 - PubMed
  65. Genes Cancer. 2010 Jan 1;1(1):50-61 - PubMed
  66. BMC Neurosci. 2008 Jan 30;9:15 - PubMed
  67. Int J Oncol. 2013 Mar;42(3):921-8 - PubMed
  68. Oncogene. 2007 Apr 12;26(17):2435-44 - PubMed
  69. Biochim Biophys Acta. 2014 Apr;1845(2):136-54 - PubMed
  70. PLoS One. 2013 Apr 30;8(4):e62042 - PubMed

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