Fig. 5. PHGDH mediates the inhibition of tumor growth in low glucose.

a, b 3-PGA binding of PHGDH controls apoptosis in liver tissues. Hepatic PHGDH mutant-expressing mice (established by injecting AAVs carrying individual PHGDH mutants) were treated with DEN plus CCl₄, as depicted in Supplementary information, Fig. S4a to induce HCC, and the livers were excised, followed by determining the p-Ser58-p53 by immunohistochemistry (IHC) (a; data are means ± SD, n = 10–13 fields from 7 mice, with P values calculated by one-way ANOVA, followed by Dunnet; Peri., peripheral) or by immunoblotting (b). See also apoptotic markers in HCC tissues in b (immunoblots) and Supplementary information, Fig. S5a, b (IHC images). T, tumor; NT, non-tumor. The scale bars are 100 μm. c Apoptosis levels are inversely correlated with levels of 3-PGA in the regions of liver tissues. Peripheral and central regions of HCC tissues were homogenized, followed by determining levels of glycolytic intermediates via CE-MS. Data are means ± SD, n  =  18–24, with P values calculated by two-way ANOVA, followed by Tukey. See levels of other glycolytic intermediates in Supplementary information, Fig. S5d. d Lack of 3-PGA binding of PHGDH inhibits tumor growth. Statistics of total tumor numbers of each mouse (upper panel; shown as means ± SD, n  =  9–15, with P values calculated by one-way ANOVA, followed by Tukey), as well as the numbers of tumor in each size/diameter: 0–2 mm, 2–4 mm, 4–6 mm, 6–8 mm, or > 8 mm (lower panel; shown as means ± SD, n  =  9–11, with P values calculated by two-way ANOVA, followed by Tukey) in each genotype, were shown. Experiments were performed three times.