Here, we demonstrated that EGFR-phosphorylated PFKP Y64 can induce VEGF expression directly through AKT activation-mediated β-catenin S552 phosphorylation and indirectly through AKT/SP1-mediated HIF-1α transcriptional expression, thereby enhancing blood vessel formation in GBM tumors (Fig. 6). Here, SP1 is linked to glioblastoma.