Fig. 6: Inhibition of PFKFB3-S172 phosphorylation by OGT is required for tumorigenesis.
From: O-GlcNAcylation of PFKFB3 is required for tumor cell proliferation under hypoxia
a A total of 3 × 106control or OGT depleted SW1990 cells with PFKFB3 depletion and reconstituted expression of the WT rPFKFB3 or rPFKFB3 S172A were subcutaneously injected into the athymic nude mice. Representative tumour xenografts were shown (left panel). Data represent the means ± s.e.m. (n = 8 mice per group, right panel). b Immunoprecipitated Flag-PFKFB3 from 8 pooled lysates of tumour tissues pool (as indicated in Fig. 6a) was subjected to immunoblotting analyses. c Immuno-histochemical staining was performed on 73 human pancreas tumour specimens. Representative images are shown. Scale bars: 50 μm. d Semi-quantitative scoring was performed (Kendall’s correlation test; R = −0.278, P = 0.0044.). e The survival times for 73 patients with low (0–2 staining scores, blue curve) versus high (3–6 staining scores, red curve) OGT (low, n = 26 patients; high, n = 47 patients) or with low (0–2 staining scores, red curve) versus high (3–6 staining scores, red curve) PFKFB3-S172 phosphorylation (low, n = 47 patients; high, n = 26 patients) (right) were compared. The Kaplan-Meier method and log-rank tests indicate the significance level of the association of OGT (p = 0.0023) with patient survival and the significance level of the association of PFKFB3-S172 phosphorylation (p = 0.0199) with patient survival. The table (lower) shows the cox-multivariate analysis after adjustment for patient sex and age, indicating the significance level of the association of OGT (p = 0.02, HR = 2.344) with patient survival duration and the significance level of the association of PFKFB3-S172 phosphorylation (p = 0.013, HR = 0.503) with patient survival duration.
