Page 78 - D. Cancer biology

[D. Cancer biology-53]

Phosphofructokinase 1 Platelet Isoform Promotes VEGF

Expression through HIF-1α-dependent and -independent

mechanisms

Je Sun Lim¹, Jong-Ho Lee¹˙²

¹Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea,

²Department of Biological Sciences, Dong-A University, Busan 49315, Republic of Korea

Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis that contributes to
tumorigenesis. However, it remains unclear whether the metabolic enzyme plays a role in the regulation of VEGF

expression. Here, we show that phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-limiting
reaction in glycolysis, promotes EGFR activation-induced VEGF expression in human glioblastoma cells. Importantly,

we demonstrate that EGFR-phosphorylated PFKP Y64 has a critical role in mRNA and protein expression of HIF-1α
a transcription factor for VEGF expression; the levels of PFKP Y64 phosphorylation are positively correlated with

HIF-1α expression in human glioblastoma specimens. In addition, EGFR-phosphorylated PFKP Y64 induces AKT-
mediated β-catenin S552 phosphorylation and subsequent β-catenin transactivation, thereby enhancing VEGF

transcriptional expression. These findings highlight a novel mechanism underlying a glycolytic enzyme-mediated
VEGF expression and underscore the potential role of PFKP on VEGF expression in HIF-1α-dependent and -

independent manners.