Cancer cells activate de novo fatty acid synthesis to provide essential structural components and substrates for the generation of signalling molecules.
Transcriptional regulators of lipid biosynthesis are downstream targets of oncogenes and tumour suppressor pathways.
Cancer cells can induce lipid uptake to respond to changes in environmental conditions.
Dependence of cancer cells on lipid synthesis or uptake may be defined by the conditions of the tumour microenvironment.
Lipid synthesis contributes to cellular processes linked to tumour progression.
Multiple lipid metabolism enzymes have been investigated as potential targets for cancer therapy.
Lipid metabolism, in particular the synthesis of fatty acids (FAs), is an essential cellular process that converts nutrients into metabolic intermediates for membrane biosynthesis, energy storage and the generation of signalling molecules. This Review explores how different aspects of FA synthesis promote tumorigenesis and tumour progression. FA synthesis has received substantial attention as a potential target for cancer therapy, but strategies to target this process have not yet translated into clinical practice. Furthermore, efforts to target this pathway must consider the influence of the tumour microenvironment.
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The authors thank B. Peck for helpful discussions and all members of the Schulze laboratory for critical reading of the manuscript. We also wish to apologize for the numerous important studies in the field of lipid metabolism in cancer that we could not cite owing to space limitations.
The authors declare no competing financial interests.
- Fatty acid synthase
(FASN). Mammalian FASN is a multifunctional enzyme containing seven catalytic domains: malonyl/acetyltransferase, β-ketoacyl-synthase, dehydrase, enoyl-ACP-reductase, β-ketoacyl-reductase, thioesterase and acyl carrier protein.
The process by which fatty acids are sequentially degraded to acetyl-CoA, which can subsequently be oxidized by the mitochondrial tricarboxylic acid cycle to produce ATP.
- E-Box sequences
Palindromic DNA element with the consensus sequence CANNTG, which is found in the promoters of many genes and mediates transcription factor binding.
- Lipid droplets
Specialized organelles rich in neutral lipids, cholesterol and cholesteryl esters.
- Lipid rafts
Highly specialized microdomains in the plasma membrane characterized by distinct lipid composition that act as platforms for the assembly of signalling molecules.
- Raman spectroscopy
A label-free spectroscopic imaging technique that can be applied to tissue sections. It is based on a characteristic shift in the frequency of light used to illuminate a specimen.
Wasting syndrome characterized by atrophy of muscle and adipose tissue and extreme weight loss.
Post-translational covalent attachment of fatty acids to amino acid side-chains of proteins. Common examples are myristoylation and palmitoylation to promote membrane association of proteins.
- WNT proteins
A family of secreted glycoproteins involved in tissue homeostasis and organ development. One pathway activated by WNT proteins is β-catenin-induced transcription.
- Epithelial-to-mesenchymal transition
(EMT). A phenotype that occurs during development as well as in cancer cells. During EMT, epithelial cells acquire mesenchymal traits, including loss of cell–cell contacts and enhanced motility, caused by altered transcription and microRNA regulation of cytoskeletal proteins.
- Non-alcoholic fatty liver disease
(NAFLD). Pathological accumulation of fat in the liver often associated with insulin resistance and the metabolic syndrome.
- Metronomic treatment regimens
Therapeutic concept describing the continuous administration of drugs at doses below the maximum tolerated dose.
- Unfolded protein response (UPR) pathway
A stress response pathway activated upon accumulation of misfolded proteins in the lumen of the endoplasmic reticulum.
- Imaging mass spectrometry
(IMS). Technique to visualize the spatial distribution of metabolites, biomarkers or proteins in a biological sample, such as a tissue section.
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Röhrig, F., Schulze, A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer 16, 732–749 (2016). https://doi.org/10.1038/nrc.2016.89
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