Figure 2
From: Colorectal cancers utilize glutamine as an anaplerotic substrate of the TCA cycle in vivo
More [13C5]-glutamine enters the TCA cycle in PIK3CA mutant tumors in subcutanous xenograft models. (A) Schematic diagram of glutamine and its metabolites in the TCA cycle. (B) Schematic diagram of mice bearing subcutanous (subcu) xenograft tumors infused with [13C5]-glutamine. Isogenic HCT116 PIK3CA WT only cells, in which the mutant allele is knocked out, were injected into left flanks of nude mice, whereas HTCT116 PIK3CA mutant only cells, in which the WT allele was knocked out, were injected into the right. Two weeks post-injection, mice (n = 8) bearing similar size tumors in the two flanks were surgically catheterized for [13C5]-glutamine infusion. (C) More glutamine enters the TCA cycle in HTC116 PIK3CA mutant tumors than in the isogenic WT tumors. The indicated metabolite was measured by GC-MS and the percentage of the 13C-labeled metabolite in the total pool was calculated. *p < 0.05, the Student’s t test. (D) A significant fraction of glutamine enters the TCA cycle in xenograft tumors. Percentages of total 13C-labeled glutamate, succinate, fumarate, malate and citrate are normalized to total 13C-labeled glutamine and plotted.
