Abstract
Abstract Cytokines and their receptors play important roles in the regulation of cell fate, inflammation and immunity. The cytokine receptor for Oncostatin M (OSMR) drives brain tumor stem cell (BTSC) proliferation and tumorigenesis. Here, we report a novel role for OSMR in regulation of cellular respiration. Genetic knockdown of OSMR in BTSCs impairs mitochondrial biogenesis and oxidative phosphorylation. Importantly, blockade of OSMR signalling in BTSCs sensitizes them to ionizing radiation and Temozolomide in vitro and in vivo. This mechanism whereby OSMR regulates mitochondrial respiration and metabolism is conserved in post-mitotic neutrons. Thus, while OSMR is required for BTSC proliferation, OSMR confers resistance to therapy via enhancing mitochondrial respiration, independent of its role in proliferation. Our data suggest that therapeutic targeting of OSMR may be beneficial to eradicate quiescent tumour stem cells and tumour relapse.
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