Figure 7. Growth of HCT-116 MTHFD2 deletion tumors requires SHMT1.
a. Serine enrichment from steady-state infusion (130 mg/kg/h) of [2,3,3-2H]serine. Serum serine isotope labeling obtained from cardiac puncture (upper left) or tail vein draw (bottom left) or from tumor metabolite extraction (bottom right) (n=7). b. Serum formate concentration and labeling in mice that did or did not receive [2,3,3-2H]serine infusion (n=4–8). c. dTTP 2H-labeling fraction from extracted tumors. M+2 dTTP is from cytosolic (SHMT1-mediated) serine-driven methylene-THF production; M+1 is from mitochondrial serine catabolism. d. Schematic showing blocked reactions and potential for formate rescue (yellow highlighting) in SHMT1/MTHFD2 double deletion cells. e. Growth of HCT-116 mthfd2Δ/shmt1Δ cells ±1 mM formate. f. Growth of shmt1Δ xenografts (n=10). g. Representative mice 8 weeks post injection of mthfd2Δ (right) and mthfd2Δ/shmt1Δ (left) cells. h. Associated tumor growth curves (mean ±SEM, n=12).