Extended Data Fig. 9: Inhibition of serine and glycine metabolism in MYC liver tumours.
From: Identifying strategies to target the metabolic flexibility of tumours
a, Representative 15N-HMBC 2D NMR signals of the indicated metabolites in mouse livers and tumours after an [amino-15N]glutamine bolus (NMR spectra acquired: n = 4 mice per group). b, 15N-enrichment of glutamine (m+1) in the serum of mice shown in Fig. 7g and Extended Data Fig. 9a,d,e (CT/control diet n = 5 mice, CT/-SG diet n = 5 mice, Psat1KO/control diet n = 7, Psat1KO/-SG diet n = 7). GC-MS. Glutamine enrichment is estimated from quantification of its spontaneous product pyroglutamate. c, Psat1fl/fl cells were transduced with either MSCV-CreER or Empty vector, and both lines were treated with 4OH-Tamoxifen to induce Cre activity. The resulting Psat1WT and Psat1KO cells were cultured in DMEM with dialysed FCS and indicated metabolites. Ser: 0.5 mM serine; Gly: 0.5 mM glycine; 0.5 mM formate. Representative curves from one of three independent experiments with three replicates are shown. Data represent mean ± S.D. d, Total concentration of metabolites in livers and tumours of mice from the experiment shown in Fig. 7f,g and Extended data Fig. 9a,b,e (normal livers/control diet n = 4 mice, normal livers/-SG diet n = 4 mice, CT tumours/control diet n = 5 mice, CT tumours/-SG diet n = 5 mice, Psat1KO tumours/control diet n = 7 mice, Psat1KO tumours/-SG diet n = 7 mice). LC-MS. e, Total concentration and 15N-enrichment from an [amino-15N]glutamine bolus in serine and glycine from the serums of the indicated mice from the experiment shown in (a) (CT/control diet n = 5 mice, CT/-SG diet n = 5 mice, Psat1KO/control diet n =7 mice, Psat1KO/-SG diet n = 7). In (b and e) data are presented as mean ± S.D. Statistical analysis was performed using a two-tailed Student’s t-test. Complete list of exact P values is provided as a source data file. In (d) data are presented as mean ± S.D. Statistical analysis was performed using one-way ANOVA followed by Tukey's post hoc test. *, P < 0.05; **, P < 0.01; ***, P < 0.001, with respect to CT tumours on control diet; #, P < 0.05; ##, P < 0.01; ###, P < 0.001, with respect to CT tumours on –SG diet.
