Novel role of tumor suppressor p53 for metabolic control and epigenetic regulation upon a metabolic response

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Recent epidemiologic evidence suggests that type 2 diabetes and obesity are at significantly higher risk for many types of cancer. In this context, p53 has been shown to control mitochondrial functions through regulation of ROS and cell metabolism, implicating its potential role in biologic links between diabetes and cancer. Here we have explored p53 targets to regulate cell metabolism using ChIP- and RNA-sequencing and identified GLS2, a key enzyme to convert glutamine to glutamate, thereby a regulator of glutathione synthesis and ATP production via TCA cycle. GLS2 overexpression inhibited cancer cell growth as well as invasion in both vitro and vivo, suggesting its potential role for tumor suppression. Thus, p53-GLS2 pathway may contribute to the common pathogenesis between life-style related diseases and cancer.