ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation

Yi Chieh Lim, Hazel Quek, Carolin Offenhäuser, Mohd Shazrul Fazry Sa`Ariwijaya, Andrew Boyd, Martin Lavin, Tara Roberts, Bryan Day

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glioblastoma (GBM) is a highly fatal disease with a 5 year survival rate of less than 22%. One of the most effective treatment regimens to date is the use of radiotherapy which induces lethal DNA double-strand breaks to prevent tumour growth. However, recurrence occurs in the majority of patients and is in-part a result of robust radioresistance mechanisms. In this study, we demonstrate that the multifunctional cytokine, interleukin-6 (IL-6), confers a growth advantage in GBM cells but does not have the same effect on normal neural progenitor cells. Further analysis showed IL-6 can promote radioresistance in GBM cells when exposed to ionising radiation. Ablation of the Ataxia-telangiectasia mutated serine/threonine kinase that is recruited and activated by DNA double-strand breaks reverses the effect of radioresistance and re-sensitised GBM to DNA damage thus leading to increase cell death. Our finding suggests targeting the signaling cascade of DNA damage response is a potential therapeutic approach to circumvent IL-6 from promoting radioresistance in GBM.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Neuro-Oncology
DOIs
Publication statusAccepted/In press - 21 Mar 2018

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Glioblastoma
Ionizing Radiation
Interleukin-6
Cell Proliferation
Double-Stranded DNA Breaks
DNA Damage
Ataxia Telangiectasia
Protein-Serine-Threonine Kinases
Growth
Cell Death
Radiotherapy
Stem Cells
Survival Rate
Cytokines
Recurrence
Therapeutics
Neoplasms

Keywords

  • Ataxia-telangiectasia mutated
  • DNA damage response
  • Glioblastoma
  • Inhibitor
  • Interleukin-6

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

Cite this

ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation. / Lim, Yi Chieh; Quek, Hazel; Offenhäuser, Carolin; Sa`Ariwijaya, Mohd Shazrul Fazry; Boyd, Andrew; Lavin, Martin; Roberts, Tara; Day, Bryan.

In: Journal of Neuro-Oncology, 21.03.2018, p. 1-10.

Research output: Contribution to journalArticle

Lim, Yi Chieh ; Quek, Hazel ; Offenhäuser, Carolin ; Sa`Ariwijaya, Mohd Shazrul Fazry ; Boyd, Andrew ; Lavin, Martin ; Roberts, Tara ; Day, Bryan. / ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation. In: Journal of Neuro-Oncology. 2018 ; pp. 1-10.
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