Metabolic regulation by p53: Implications for cancer therapy

The tumor suppressor p53, long known for its roles in maintaining genomic integrity and suppressing tumorigenesis, has recently been recognized as a key regulator of cellular metabolism. Here, we review p53's emerging metabolic functions, highlighting its ability to orchestrate glucose, amino acid, and lipid metabolism. By promoting oxidative phosphorylation while inhibiting glycolysis and anabolic pathways, wild-type p53 counters metabolic reprogramming characteristic of cancer cells, such as the Warburg effect, and protects cells from mild cellular stresses. In contrast, mutant p53 disrupts these processes, fostering metabolic adaptations that support tumor progression. These findings pave the way for therapeutic approaches targeting p53-driven metabolic vulnerabilities in cancer.