Fig. 3: Tumor respiration defect sensitizes NSCLC to serine/glycine starvation.

A Experimental design schematic: Old and young KP, WT, PGKP, and PolG animals were infected with adenovirus-Cre. After 15 weeks, euthanasia was performed, and plasma, NSCLC tumors (only KP and PGKP develop NSCLC), and normal lungs (from WT and PolG) were collected. The gathered material underwent pool-size metabolomics and glucose meter measurements. B Blood glucose levels. C Survival curve and median survival of KP and PGKP animals under a high carbohydrate diet (70% sucrose). D, E Representative volcano plot and pathway impact analysis for pool-size metabolomics comparing old KP and PGKP tumors. f, g Serine and GSH levels are shown for normal lungs (WT and PolG) and NSCLC tumors (PGKP and KP) at different ages. n indicates the number of animals for solid tissue for both, serine and GSH. H, I Serine and GSH plasma levels. n indicates the number of animals for plasma for both, serine and GSH. j Survival curve and median survival of KP and PGKP animals under amino acid control (AA-crtl) and serine/glycine-free diet. In B and F-I, individual sample distributions are represented by dots, while the gray bar indicates the median ± SEM. Two-tailed t-tests determined P values for C (median survival), while one-way ANOVA with Tukey correction was used in B, C, and F-J. Log-rank (Mantel-Cox) calculated P values for survival curves C and J. Significance levels are denoted as *≤0.05, **≤0.01, ***≤0.001, and ****≤0.0001. Only the relevant statistics are displayed in the figures. For detailed individual P  values, please refer to the Source Data table. The Figures A, C and J were created in Biorender. Cararo Lopes, E and White, E (2025).