Page 76 - D. Cancer biology

[D. Cancer biology-52]

Phosphofructokinase 1 platelet isoform promotes β-catenin

activation for tumor development

Jong-Ho Lee¹˙²

¹Department of Biological Sciences, Dong-A University, Busan 49315, Republic of Korea, ²Department of Health

Sciences, the Graduate School of Dong-A University, Busan 49315, Republic of Korea

Metabolism plays a critical role in direct regulation of a variety of cellular activities via metabolic enzymes and
metabolites. Here, we demonstrate that phosphofructokinase 1 platelet isoform (PFKP), which catalyzes a rate-

limiting reaction in glycolysis, promotes EGFR activation-induced nuclear translocation and activation of β-catenin,

thereby enhancing the expression of its downstream genes CCND1 and MYC in human glioblastoma cells.
Importantly, we showed that EGFR-phosphorylated PFKP Y64 has a critical role in AKT activation and AKT-mediated
β-catenin S552 phosphorylation and subsequent β-catenin transactivation and promotion of tumor cell glycolysis,

migration, invasion, proliferation, and brain tumor growth. These findings highlight a novel mechanism underlying
a glycolytic enzyme-mediated β-catenin transactivation and underscore the integrated and reciprocal regulation of

metabolism and gene expression, which are two fundamental biological processes in tumor development.