Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets

Sze Kiat Tan; Helen Y Hougen; Jaime R Merchan; Mark L Gonzalgo; Scott M Welford

doi:10.1038/s41585-022-00654-6

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Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets

Journal article

Peer reviewed

Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets

Sze Kiat Tan, Helen Y Hougen, Jaime R Merchan, Mark L Gonzalgo and Scott M Welford

Nature reviews. Urology, Vol.20(1), pp.48-60

01/01/2023

DOI: 10.1038/s41585-022-00654-6

PMCID: PMC10826284

PMID: 36192502

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10826284/pdf/nihms-1959763.pdfView

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Abstract

Lipid droplet formation is a defining histological feature in clear-cell renal cell carcinoma (ccRCC) but the underlying mechanisms and importance of this biological behaviour have remained enigmatic. De novo fatty acid (FA) synthesis, uptake and suppression of FA oxidation have all been shown to contribute to lipid storage, which is a necessary tumour adaptation rather than a bystander effect. Clinical studies and mechanistic investigations into the roles of different enzymes in FA metabolism pathways have revealed new metabolic vulnerabilities that hold promise for clinical effect. Several metabolic alterations are associated with worse clinical outcomes in patients with ccRCC, as lipogenic genes drive tumorigenesis. Enzymes involved in the intrinsic FA metabolism pathway include FA synthase, acetyl-CoA carboxylase, ATP citrate lyase, stearoyl-CoA desaturase 1, cluster of differentiation 36, carnitine palmitoyltransferase 1A and the perilipin family, and each might be potential therapeutic targets in ccRCC owing to the link between lipid deposition and ccRCC risk. Adipokines and lipid species are potential biomarkers for diagnosis and treatment monitoring in patients with ccRCC. FA metabolism could potentially be targeted for therapeutic intervention in ccRCC as small-molecule inhibitors targeting the pathway have shown promising results in preclinical models.

Carcinoma, Renal Cell - pathology

Fatty Acids - metabolism

Humans

Kidney Neoplasms - pathology

Lipid Metabolism - genetics

Lipids

Details

Title: Subtitle: Fatty acid metabolism reprogramming in ccRCC: mechanisms and potential targets
Creators: Sze Kiat Tan - University of Miami
Helen Y Hougen - University of Miami
Jaime R Merchan - University of Miami
Mark L Gonzalgo - University of Miami
Scott M Welford - University of Miami
Resource Type: Journal article
Publication Details: Nature reviews. Urology, Vol.20(1), pp.48-60
DOI: 10.1038/s41585-022-00654-6
PMID: 36192502
PMCID: PMC10826284
NLM abbreviation: Nat Rev Urol
ISSN: 1759-4812
eISSN: 1759-4820
Grant note: R01 CA254409 / NCI NIH HHS
Language: English
Date published: 01/01/2023
Academic Unit: Urology
Record Identifier: 9984701542702771

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