Figure 3. Alteration of key metabolic enzymes for the de novo fatty acids biosynthesis in HCT116 colorectal cancer cells in hypoxia.

(a) Metabolic pathways of acetyl-CoA forming sterol, fatty acid synthesis or acetate, and enzymes involved. FASN mediated de novo fatty acids biosynthesis precedes the formation of the main classes of complex lipids. (b) Acetate (product of acetyl-CoA catabolism) was detected by ¹H-NMR in the aqueous phase. Intensities are shown as normalized relative intensities and reported as mean ±sd (n=3). (c and d) Label-free quantitative proteomics analysis reveals altered levels of key metabolic enzymes: Acetyl-CoA carboxylase 1 and Acetyl-CoA acetyltransferase 1. Data are shown as mean ±sd of normalized intensities (n=3). (e) Western blot analysis was used to confirm the pattern of regulation of ACC1. Western blot analysis assessing the hypoxic response of FASN and SREBP-1 in wild type and hif1α^−/−, HCT116 colorectal cancer cells (n=3).