p53-Mediated Metabolic Regulation in Cancer Cells

The tumour suppressor p53 is widely recognised for its role in DNA damage response and cell cycle control, yet emerging evidence has highlighted its pivotal involvement in cellular metabolism. In cancer cells, p53 coordinates a network of metabolic pathways to limit proliferation and promote cell death under stress conditions. By modulating glycolysis, oxidative phosphorylation, lipid turnover and nucleotide synthesis, p53 ensures metabolic flexibility and energy homeostasis. Loss or mutation of p53 disrupts these regulatory circuits, favouring the Warburg effect, unchecked biosynthesis and accumulation of reactive oxygen species. Recent work reveals that p53 not only represses pro-tumorigenic pathways such as aerobic glycolysis and the pentose phosphate pathway but also enhances counter-oncogenic processes including fatty acid β-oxidation and gluconeogenesis. Through transcriptional activation or repression of key metabolic enzymes and cofactors, p53 integrates nutrient sensing with stress signalling to restrain tumour growth. Understanding these multifaceted roles offers novel therapeutic avenues aimed at reinstating p53 function or targeting its metabolic effectors in diverse cancer types.

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p53-Mediated Metabolic Regulation in Cancer Cells publication trend

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Technical terms

p53: A protein that suppresses tumours by controlling cell cycle arrest, apoptosis and diverse metabolic pathways.

Glycolysis: The enzymatic breakdown of glucose to pyruvate, yielding ATP and biosynthetic precursors.

Oxidative phosphorylation: Mitochondrial process generating ATP through the electron transport chain and oxygen consumption.

Fatty acid β-oxidation: The sequential removal of two-carbon units from fatty acids to produce acetyl-CoA for energy production.

Acetyl-CoA: A central metabolite that links carbohydrate, lipid and protein metabolism and serves as a substrate for acetylation reactions.

References

1. p53 promotes peroxisomal fatty acid β-oxidation to repress purine biosynthesis and mediate tumor suppression. Cell Death & Disease (2023).
2. p53 and metabolism: from mechanism to therapeutics. Oncotarget (2018).
3. p53 as a Regulator of Lipid Metabolism in Cancer. International Journal of Molecular Sciences (2016).
4. p53 promotes the expression of gluconeogenesis-related genes and enhances hepatic glucose production. Cancer & Metabolism (2013).