Abstract
Abstract Oncostatin M Receptor (OSMR) is a key regulator of brain tumour stem cell (BTSC) self-renewal and glioblastoma (GB) tumourigenesis. This receptor is found in a complex with Epidermal Growth Factor Receptor variant III (EGFRvIII) and orchestrates a positive feedback loop with STAT3. OSMR also regulates oxidative phosphorylation and participates in promoting the transition of cells towards mesenchymal-like glioma states. How OSMR drives GB tumorigenesis via multiple mechanisms remains largely unclear. Here, we map OSMR interactome in different GB subtypes using the Mammalian Membrane Two Hybrid High Throughput Screen (MaMTH-HTS). Analysis of these data followed by functional validation has uncovered distinct OSMR interactome in a context dependent manner. Follow up investigations, however, have led to the discovery of the Chloride Intracellular Channel 1 (CLIC1), essential in the regulation of OSMR cytokine signaling and GB progression independently of the genetic profile of the GB tumour. CLIC1 forms a complex with OSMR to promote BTSC self-renewal and knockout of CLIC1 or pharmacological inhibitors to CLIC1 impairs OSM mediated STAT3 phosphorylation. Our work suggests that CLIC1 and OSMR form a complex in BTSCs and functionally interact to activate STAT3.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
