Metabolic alterations are common features of cancer cells and have recently been shown to have an important role in the maintenance of malignancies.
p53 is a key tumour suppressor protein that has a diverse range of functions — including the ability to promote apoptosis, senescence and DNA repair — each of which helps to prevent cancer development. A role for p53 in regulating metabolic pathways has also recently been identified, suggesting that this is another mechanism by which p53 helps to stall malignant progression.
Several functions of p53 promote oxidative phosphorylation and dampen glycolysis in cells; disruption of this balance is associated with mutations in p53 and oncogenic transformation.
p53 also has a key role in regulating cell growth and autophagy, thereby helping to coordinate the cell's response to nutrient starvation.
Altered metabolism can contribute to malignant transformation, and cancer cells become dependent on these changes. Understanding the role of p53 in the regulation of metabolism may provide some interesting potential targets for the development of new cancer therapies.
Although metabolic alterations have been observed in cancer for almost a century, only recently have the mechanisms underlying these changes been identified and the importance of metabolic transformation realized. p53 has been shown to respond to metabolic changes and to influence metabolic pathways through several mechanisms. The contributions of these activities to tumour suppression are complex and potentially rather surprising: some reflect the function of basal p53 levels that do not require overt activation and others might even promote, rather than inhibit, tumour progression.
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We would like to thank E. Gottlieb and E. Cheung for reading the manuscript and support from Cancer Research UK.
The stepwise pathway that converts glucose into pyruvate with the net generation of two molecules of ATP.
Literally translated from greek as 'self eating'. The cellular trafficking process whereby cytoplasmic constituents are targeted to lysosomes for degradation.
A decrease in ambient O2 availability and levels.
- Oxidative stress
The accumulation of ROS owing to increased production, the inability of the cell to counter ROS production or both.
The metabolic pathway that breaks down glutamine.
The metabolic breakdown of relatively complex molecules into simpler parts.
A less ordered form of cell death that is characterized by cell rupture and, in an organismal setting, an inflammatory response.
The selective degradation of mitochondria by autophagy.
The aspect of metabolism in which more complex molecules are built from their constituent parts, such as proteins from amino acids.
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Vousden, K., Ryan, K. p53 and metabolism. Nat Rev Cancer 9, 691–700 (2009). https://doi.org/10.1038/nrc2715
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