More importantly, as PDGFD, PDGFRα, and HIF1α were all required for GBM cell growth and invasion under normoxia and in xenografted mice, our work implies that the PDGFD-PDGFRα-HIF1α axis could be an essential event for GBM malignancy, which is predominantly functional under normoxic or mildly hypoxic conditions. Here, PDGFD is linked to glioblastoma.