Extended Data Fig. 7: Glucose consumption and 2-DG sensitivity in KRAS-mutant human tumour cells with or without exon 4A.
a, Rate of glucose consumption (mean ± s.e.m.; n = 3) in parental (4A+/+) and exon 4A-targeted (4A−/−) A549 cells transfected with Flag–GFP or Flag–KRAS4A(G12V). Representative expression is shown by immunoblot. b, Flux of lactate secretion (mean ± s.e.m.; n = 3) measured over 24 h in A549 cells with the indicated genotype. c, Incorporation of 13C from glucose into lactate (mean ± s.e.m.; n = 3) in A549 cells with the indicated genotype. Significance in a–c was determined by paired Student’s t-test. d, e, Growth inhibition by 2-DG of SUIT2 (d; 48 h) and A549 (e; 24 h) cells with or without the 4A exon of KRAS (mean ± s.e.m.; n = 3; significance by two-way ANOVA). f, g, SUIT2 (f) or A549 (g) cells were used to establish xenograft tumours on the contralateral flanks (4A+/+ versus 4A−/−) of NCG mice. Six weeks later, when the tumours were established and of equivalent size, glucose uptake was measured by 18F-FDG-PET CT scan. f, Left, coronal scan of a representative mouse with SUIT2 xenografts. Glucose uptake is represented by a colour look-up table. Right, SUVs of the entire tumour are plotted (mean ± s.d.; n = 5 mice; significance by two-way ANOVA) as a function of time after 18FDG injection. g, Left, coronal scan of a representative mouse (of n = 5 mice) with A549 xenografts. Right, SUV versus time after injection or that mouse.
