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

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

Research output: Contribution to journalArticlepeer-review

9 Citations (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)509-518
Number of pages10
JournalJournal of Neuro-Oncology
Volume138
Issue number3
DOIs
Publication statusPublished - 1 Jul 2018

Bibliographical note

Publisher Copyright:
© 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Keywords

  • cells
  • glioblastoma
  • gliomas
  • interleukin-6

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