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

最近的流行病学证据表明，2型糖尿病和肥胖症对许多类型的癌症的风险都要高得多。在这种情况下，p53已被证明通过调节ROS和细胞代谢来控制线粒体功能，暗示其在糖尿病和癌症之间的生物学联系中的潜在作用。本研究利用ChIP-和rna测序技术探索了p53调控细胞代谢的靶点，发现GLS2是谷氨酰胺转化为谷氨酸的关键酶，通过TCA循环调节谷胱甘肽合成和ATP生成。GLS2过表达在体外和体内均能抑制癌细胞的生长和侵袭，提示其具有潜在的抑瘤作用。因此，p53-GLS2通路可能参与了生活方式相关疾病与癌症的共同发病机制。

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.