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[A. Biochemistry/Molecular Biology] A-16
Mutual Regulation between Phosphofructokinase 1 platelet
isoform and VEGF Promotes Glioblastoma Tumor Growth
Je Sun Lim¹, Jong-Ho Lee¹,²*
¹Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea, ²Department of
Biological Sciences, Dong-A University, Busan 49315, Korea
Glioblastoma (GBM) is highly vascular malignant brain tumor that overexpresses vascular endothelial growth factor
(VEGF) as well as phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting reaction in glycolysis.
However, it remains unknown whether PFKP and VEGF are reciprocally regulated during GBM tumor growth. Here,
we show that PFKP promotes EGFR activation-induced VEGF expression in HIF-1α-dependent and -independent
manners in GBM cells. Importantly, we demonstrate that EGFR-phosphorylated PFKP Y64 has critical roles in
AKT/SP1-mediated transcriptional expression of HIF-1α and in AKT-mediated β-catenin S552 phosphorylation, to
fully enhance VEGF transcription and subsequent blood vessel formation and brain tumor growth. Conversely, VEGF
upregulates PFKP expression in a PFKP S386 phosphorylation-dependent manner, leading to increased PFK enzyme
activity, aerobic glycolysis, and proliferation of GBM cells. These findings highlight a novel mechanism underlying
the mutual regulation that occurs between PFKP and VEGF for promoting GBM tumor growth and underscores that
cancer cells’ fundamental biological processes, metabolism, and other cellular activities, are integrated and mutually
regulated in promoting tumor development.
