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Review
. 2016 Dec 10;17(12):2074.
doi: 10.3390/ijms17122074.

p53 as a Regulator of Lipid Metabolism in Cancer

Alejandro Parrales  1 , Tomoo Iwakuma  2
Affiliations
Review

p53 as a Regulator of Lipid Metabolism in Cancer

Alejandro Parrales et al. Int J Mol Sci. .

Abstract

Enhanced proliferation and survival are common features of cancer cells. Cancer cells are metabolically reprogrammed which aids in their survival in nutrient-poor environments. Indeed, changes in metabolism of glucose and glutamine are essential for tumor progression. Thus, metabolic reprogramming is now well accepted as a hallmark of cancer. Recent findings suggest that reprogramming of lipid metabolism also occurs in cancer cells, since lipids are used for biosynthesis of membranes, post-translational modifications, second messengers for signal transduction, and as a source of energy during nutrient deprivation. The tumor suppressor p53 is a transcription factor that controls the expression of proteins involved in cell cycle arrest, DNA repair, apoptosis, and senescence. p53 also regulates cellular metabolism, which appears to play a key role in its tumor suppressive activities. In this review article, we summarize non-canonical functions of wild-type and mutant p53 on lipid metabolism and discuss their association with cancer progression.

Keywords: cancer; fatty acid oxidation; lipid metabolism; mevalonate pathway; p53.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Regulation of lipid metabolism by wild-type and mutant p53. (A) Schematic representation of functional domains in p53 and regions which interact with G6PD and AMPKα. TA: transactivation domain, DBD: DNA-binding domain, TD: tetramerization domain, RD: regulatory domain; (B) Wild-type p53 (wtp53) can regulate lipid metabolism by direct protein–protein interaction or transcriptional control of proteins involved in fatty acid synthesis, fatty acid oxidation, the mevalonate pathway, cholesterol efflux, and lipid droplet formation. Generally, wtp53 inhibits the fatty acid synthesis and lipid accumulation. In contrast, mutant p53 (mutp53) enhances fatty acid synthesis by inhibitory interaction with AMPKα. Also, mutp53 cooperates with SREBPs to upregulate enzymes involved in the mevalonate pathway.
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