(A) IHC staining of 57 human GBM specimens was performed with the indicated antibodies. Representative images from the staining of 5 different specimens are shown. High-magnification images correspond to the areas marked by yellow dotted lines. Scale bar, 100 μm.
(B) IHC stains were scored, and the correlation analyses were performed. Pearson correlation test was used. Note that the scores of some samples overlap.
(C) Kaplan-Meier plots of the overall survival rates in human GBM specimens (n = 57) in the groups with high (staining score, 4–8) and low (staining score, 0–3) expression of EGFR pY1068, PFKP pY64, and PFK2 pS483. p values were calculated by using the log-rank test.
(D) Mechanism of EGF-induced and PFKP phosphorylation-dependent PI3K activation. EGFR activation results in KAT5-mediated PFKP K395 acetylation and subsequent translocation of PFKP to the plasma membrane, where EGFR phosphorylates PFKP at Y64. PFKP pY64 binds to the N-terminal SH2 domain of p85α for PI3K and subsequent AKT activation. AKT phosphorylates PFK2 for enhanced fructose-2,6-BP production and PFK1 activation. PFKP Y64 phosphorylation–enhanced PI3K/AKT-dependent PFK1 activation and GLUT1 expression promote the Warburg effect.