Glioblastoma (GBM) is the most common and aggressive form of primary brain tumour with an average incidence of 3.19 per 100,000 population. The median survival time for GBM patients post diagnosis is only 14-15 months. The current standard of care for GBM patients includes maximal surgical removal, followed by concurrent chemoradiotherapy with temozolomide. While these therapies extend median patient survival, recurrence within 6-9 months is common with no effective therapy. Thus, novel treatment strategies that have greater specificity and efficacy are warranted. Analysing the Ivy Glioblastoma Atlas Project's transcriptomics data based on anatomic structures (http://www.brain-map.org/), we identified that CD47, a ubiquitously expressed receptor known to block phagocytosis by interacting with SIRPĪ± on myeloid cells, is abundantly expressed on the leading invasive edge of GBM patient tumours. Increased expression of CD47 is also associated with poorer survival in GBM patients. To date, various CD47-blocking antibodies have been developed to target several solid and haematological cancers with limited efficacy. Importantly, the role of CD47 in GBM besides promoting immune escape is not well understood. In our study, we have found that loss of CD47 in GBM cells reduces cell migration and proliferation in the absence of myeloid cells, suggesting a cell autonomous function of CD47. Consistently, gene set enrichment following transcriptomics analysis in control and CD47 knock out GBM cells indicates that cell polarity, axonal guidance, cell differentiation and cell proliferation pathways are driven by CD47 signaling. Furthermore, our data shows that CD47 regulates metabolic plasticity. We found that CD47 knock out cells exhibit elevated levels of several glycolytic metabolites which correlates with increased mitochondrial spare respiratory capacity and mitochondrial biogenesis. Thus, we have identified a novel role of CD47 in linking cellular and metabolic plasticity.