PHGDH and hepatocellular carcinoma: Moreover, a strong correlation between hyperglycemia and hepatocarcinogenesis has been established in human patients,67 and dietary restriction significantly decreases the risk of incident HCC,68 in line with the findings that low PHGDH protein expression69 prevents apoptosis and hence drives metastatic dissemination during tumor metastasis in which the levels of 3-PGA are low.70 It thus stands to reason that it is the occupancy of the substrate 3-PGA that determines PHGDH to modulate p53 pro-apoptotic activity via controlling the phosphorylation of Ser46.