Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells

• Brain cancer is one of the deadliest human tumors and is characterized by several genetic changes leading to impairment of tumor suppressive pathways and oncogene activation. These genetic alterations promote subsequent molecular changes, including modifications of cellular metabolism, which are believed to contribute to cancer pathogenesis. Conversely, the role of metabolic changes in regulation of genomic stability in brain cancer has not been investigated. Our work shows that alterations of mitochondrial metabolism promote genetic loss of the p53 tumor suppressor and transformation via a mechanism involving reactive oxygen species. Overall, our findings suggest a causative link between metabolic alterations and loss of tumor suppressive control in the central nervous system, with implications for our understanding of brain cancer pathogenesis.

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