CD47 activates ROBO2 signaling to regulate glioblastoma cell plasticity and metabolism

Although CD47-blocking antibodies have shown promise in treating various malignancies, their efficacy in glioblastoma (GBM) remains limited, and the role of CD47 beyond immune escape is poorly understood. Here, we show that CD47 is highly expressed at the invasive edge of GBM tumours, with elevated expression correlating with poorer patient survival.

We demonstrate that CD47 loss reduces proliferation, migration, and invasion, independently of immune activity leading to decreased GBM tumour burden and prolonged survival in vivo. Mechanistically, our study reveals that CD47 regulates ROBO2 signaling and enhances mitochondrial respiration. Furthermore, we demonstrate that combined loss of CD47 or ROBO2 with inhibition of mitochondrial function significantly increases GBM cell death.