Fig. 5: The GAPDH redox switch protects tumour cells in vivo.
From: The GAPDH redox switch safeguards reductive capacity and enables survival of stressed tumour cells
a, Growth of xenograft tumours after subcutaneous injection of HAP1 cells expressing either WT or mutant (Y314F) GAPDH. Based on n = 6 mice per group. Solid lines represent the mean, dotted lines represent the standard error of the mean. b, Weight of tumours explanted 28 days after xenografting. Data are presented as mean ± standard deviation (s.d.), based on n = 5 mice per group. ***P < 0.001; P = 0.0002, based on a two-tailed unpaired t-test. c, Survival time of tumour-bearing mice until reaching humane endpoints. Based on n = 17 (WT) and n = 9 (Y314F) mice. d, The roGFP2-Orp1 405 nm/488 nm fluorescence ratio as measured in cells isolated from explanted WT and mutant tumours. Data are presented as mean ± s.d., based on n = 15 (WT) and n = 8 (Y314F) mice. ****P < 0.0001, based on a two-tailed unpaired t-test. e, Metabolic flux analysis following tail vein injection of [1,2-13C]glucose and subsequent tumour explantation. The partitioning of glucose flux into glycolysis and PPP is indicated by the ratio of singly and doubly labelled F6P (left) and G3P (right). Data are presented as mean ± s.d, based on n = 5 mice per group. ***P < 0.001; P = 0.0007 and 0.0008, based on a two-tailed unpaired t-test. f, Metabolic flux analysis following tail vein injection of [1,2-13C]glucose and subsequent tumour explantation. The influx of [1,2-13C]glucose into the PPP is indicated by mass shifts in the PPP intermediates 6PG (left), R5P (middle) and S7P (right). Data are presented as mean ± s.d., based on n = 5 mice per group. ****P < 0.0001, based on a two-tailed unpaired t-test. g, NADPH/NADP+ ratio in WT and mutant tumours as determined by mass spectrometry. Data are presented as mean ± s.d., based on n = 5 mice per group. *P < 0.05; P = 0.0488, based on a two-tailed unpaired t-test.
