OSMR INTERACTOME MAPPING REVEALS THE SIGNIFICANCE OF A CHLORIDE CHANNEL IN CYTOKINE REGULATION AND BRAIN TUMOUR STEM CELL SELF-RENEWAL

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