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OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation

Author

Listed:
  • Ahmad Sharanek

    (Jewish General Hospital)

  • Audrey Burban

    (Jewish General Hospital)

  • Matthew Laaper

    (Jewish General Hospital
    Montreal Neurological Institute)

  • Emilie Heckel

    (Pharmacology and Ophthalmology, Université de Montréal, CHU Sainte-Justine
    McGill University)

  • Jean-Sebastien Joyal

    (Pharmacology and Ophthalmology, Université de Montréal, CHU Sainte-Justine
    McGill University)

  • Vahab D. Soleimani

    (Jewish General Hospital
    McGill University, 3640 Rue University)

  • Arezu Jahani-Asl

    (Jewish General Hospital
    Montreal Neurological Institute
    McGill University)

Abstract

Glioblastoma contains a rare population of self-renewing brain tumor stem cells (BTSCs) which are endowed with properties to proliferate, spur the growth of new tumors, and at the same time, evade ionizing radiation (IR) and chemotherapy. However, the drivers of BTSC resistance to therapy remain unknown. The cytokine receptor for oncostatin M (OSMR) regulates BTSC proliferation and glioblastoma tumorigenesis. Here, we report our discovery of a mitochondrial OSMR that confers resistance to IR via regulation of oxidative phosphorylation, independent of its role in cell proliferation. Mechanistically, OSMR is targeted to the mitochondrial matrix via the presequence translocase-associated motor complex components, mtHSP70 and TIM44. OSMR interacts with NADH ubiquinone oxidoreductase 1/2 (NDUFS1/2) of complex I and promotes mitochondrial respiration. Deletion of OSMR impairs spare respiratory capacity, increases reactive oxygen species, and sensitizes BTSCs to IR-induced cell death. Importantly, suppression of OSMR improves glioblastoma response to IR and prolongs lifespan.

Suggested Citation

  • Ahmad Sharanek & Audrey Burban & Matthew Laaper & Emilie Heckel & Jean-Sebastien Joyal & Vahab D. Soleimani & Arezu Jahani-Asl, 2020. "OSMR controls glioma stem cell respiration and confers resistance of glioblastoma to ionizing radiation," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17885-z
    DOI: 10.1038/s41467-020-17885-z
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