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Cancer metabolism has drawn widespread attention since the unique metabolic properties of cancer cells were characterized. We found that p53, a potent tumor suppressor, down-regulates the expression of phopshoenolpyruvate carboxykinase (PEPCK, PCK1) in coordination with histone deacetylase sirtuin 6 (SIRT6) to inhibit tumor cell gluconeogenesis (1). Because p53 is malfunctioning in numerous types of cancer, the p53-SIRT6-forkhead box protein O1 (FoxO1) axis may shed light on the “Warburg effect,” a phenomenon in cancer metabolism that has harassed scientists for decades. PCK1 is mainly expressed in liver and kidney, with an increasing expression and maturation after birth. PCK1 …

Reply to Leithner et al.: Focus on phopshoenolpyruvate carboxykinase (PEPCK): A target of the p53-SIRT6-FoxO1 axis