PCK1 and cancer: PEPCK (PCK1 or PCK2), which is traditionally associated with gluconeogenesis, also regulates TCA cycle flux and increases glucose and pyruvate utilization for anabolic metabolism.[28a] PCK2 is downregulated in human HCC.[31] However, PCK2 activation is critical for cancer cell adaptation to environmental stresses such as glucose depletion, providing a metabolic advantage under such conditions.