Extended Data Fig. 8: Inhibition of lipid metabolism in MYC liver tumours.
From: Identifying strategies to target the metabolic flexibility of tumours
a, 13C-enrichment of fatty acids (total fraction) from the indicated tissues of mice infused with [U-13C]glucose demonstrating a total blockade in fatty acid biosynthesis in FasnKO tumours (normal livers n = 4 mice, CT tumours n = 5 mice, FasnKO tumours n = 5 mice). A representative chromatogram of the fatty acid composition of a FasnKO tumour is shown. For unsaturated fatty acids, a residual enrichment that remained in the authentic standards after substraction of the natural abundance of 13C, was also substracted from the samples. b, Total fatty acid content in CT (n = 11 mice) and FasnKO (n = 10 mice) tumours. (c) Fatty acid ratios in CT (n = 11 mice) and FasnKO (n = 10 mice) tumours. d, Left panel, a heat map demonstrating the expression of genes involved in lipid transport in MYC-driven liver tumours compared to normal livers (gene microarray, Log2-transformed; n=4 mice per group). Right panel, absolute values are shown to identify those genes with higher total expression level, and to discriminate the genes with low levels of expression, which could be insufficient to produce relevant protein levels. Based on the expression of the relevant control genes (examples are shown in the lower panel) we considered 6 as a baseline level, while higher than 8 as a high level of expression. e, Total fatty acid content in CT (n = 6 mice) and FasnKO (n = 11 mice) tumours kept on the Low-Fat diet. f, The ratios of different fatty acids in CT (n = 6 mice) and FasnKO (n = 11 mice) tumours kept on the low-fat diet. 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. g, Light microscopy images of living cells isolated from CT and FasnKO tumours, after being maintained in the indicated media conditions with modulation of the lipid availability for 72 h. Representative images from three independent experiments are shown.
