Fig. 4: NSCLC rewires glycolytic metabolism to synthesize more serine from glucose.
From: Respiration defects limit serine synthesis required for lung cancer growth and survival
a Schematic depicting glycolysis→TCA with 13C distribution on pathway intermediates using [U-13C]-glucose. Intermediates include Fructose 6-phosphate (F6P), glyceraldehyde 3-phosphate (GAP), 3-phosphoglycerate (3PG). b Schematic experimental design for in vivo isotope tracing with [U-13C]-glucose infusion. KP, PGKP, WT, and PolG animals were infected with adenovirus-Cre and maintained on AA-crt or serine/glycine-free diets for 12 weeks. After fasting for six hours, animals underwent 2h30 of [U-13C]-glucose infusion and were then euthanized. Muscle, liver, plasma, and tumors or lungs were snap frozen. The collected samples were subjected to pool-size metabolomics, and tissue metabolite enrichment or isotopologue were normalized by the plasma glucose enrichment of the corresponding animal. c, d Dilution of 13C across the first cycle of glycolysis→TCA intermediates in normal (cancer-free) lungs and NSCLC tissues of mice infused with [U-13C]-glucose. e Statistical analysis of the main altered metabolites enrichment presented in D. f Serine M + 3 fractions (first turn of glycolysis→SSP). g Total pool size levels of serine in lung, tumor, and their matched plasma. The experiment was conducted with the following number of animals per group: WT = 5, WT-SG = 7, PolG = 6, PolG-SG = 6, KP = 5, KP-SG = 7, PGKP = 7, and PGKP-SG = 8. For animals with tumors, metabolites were extracted from two independent tumors per animal. For animals without tumors, metabolites were extracted from two independent lung lobes per animal. Data is shown as ± SEM. For all graphs, the P values were determined using one-way ANOVA with Tukey correction. P values are indicated as ≤0.05*, ≤0.01**, ≤0.001***, and ≤0.0001****. For detailed individual P values, please refer to the Source Data table. The Figure b was created in Biorender. Cararo Lopes, E and White, E (2025).
