Page 80 - D. Cancer biology

[D. Cancer biology-54]

Wnt-EGFR signaling induces tumor development in part

through Phosphofructokinase 1 platelet isoform upregulation

So Mi Jeon¹, 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

Activation of Wnt signaling is detected in various types of cancer and is associated with development of cancer. In
this study, we show that Wnt3A-induced EGFR transactivation plays important roles in the Warburg effect,

proliferation, and colony formation in cancer cells. Importantly, we demonstrate that Wnt3A induces

phosphofructokinase 1 (PFK1) enzyme activity, which catalyzes a rate-limiting reaction in glycolysis, specifically by
increased PFKP (platelet isoform of PFK1) expression in a β-catenin-independent manner. Wnt3A-EGFR signaling-
activated AKT stabilizes PFKP through PFKP S386 phosphorylation and subsequent PFKP upregulation. Wnt3A-

induced PFKP S386 phosphorylation increases PFKP expression and promotes the Warburg effect, cell proliferation,
and colony formation in cancer cells. These findings underscore the potential role of PFKP in Wnt signaling-induced

tumor development.