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

Ahmad Sharanek, Audrey Burban, Matthew Laaper, Emilie Heckel, Jean-Sebastien Joyal, Vahab D. Soleimani and Arezu Jahani-Asl ()
Additional contact information
Ahmad Sharanek: Jewish General Hospital
Audrey Burban: Jewish General Hospital
Matthew Laaper: Jewish General Hospital
Emilie Heckel: Pharmacology and Ophthalmology, Université de Montréal, CHU Sainte-Justine
Jean-Sebastien Joyal: Pharmacology and Ophthalmology, Université de Montréal, CHU Sainte-Justine
Vahab D. Soleimani: Jewish General Hospital
Arezu Jahani-Asl: Jewish General Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17885-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17885-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17885-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().