Characterization of metabolic landscape in hepatocellular carcinoma

Figure 1 Hepatocellular carcinoma develops two distinct lipid metabolism patterns depending on the environment or genetic background of tumor cells. A: In most conditions including hypoxia environment, and steatohepatitic or nonalcoholic steato-hepatitis-driven hepatocellular carcinoma (HCC), β-oxidation is repressed to avoid excessive oxidative damage; B: In HCC harboring β-catenin mutation, β-oxidation is promoted to trigger HCC. CACT: Carnitine–acylcarnitine translocase; CPT1: Carnitine palmitoyltransferase 1; CPT2: Carnitine palmitoyltransferase 2; FA: Fatty acid; HCC: Hepatocellular carcinoma; HIF-1α: Hypoxia inducible factor 1 subunit alpha; LCAD: Long-chain acyl-CoA dehydrogenases; MCAD: Medium-chain acyl-CoA dehydrogenases; MUFA: Monounsaturated fatty acid; PPARα: Peroxisome proliferator activated receptor alpha; SCD: Stearoyl-CoA desaturase.

Figure 2 Two distinct principles governing glutamine metabolism in hepatocellular carcinoma. A: Glutaminolysis in MYC-induced hepatocellular carcinoma (HCC) is enhanced via increasing transport and catabolism to fuel Krebs cycle; B: In HCC bearing β-catenin mutation, glutamine accumulation in response to glutamine synthetase upregulation further activates phosphorylated mammalian target of rapamycin. GLS1: Kidney-type glutaminase; GLS2: Liver type glutaminase; Gln: Glutamine; GS: Glutamine synthetase; SLC1A5: Solute-linked carrier family A1 member 5; p-4EBP1: Phosphorylated 4E-binding protein 1; p-mTOR: Phosphorylated mammalian target of rapamycin.