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Sci Transl Med. 2019 Feb 6;11(478). pii: eaau5758. doi: 10.1126/scitranslmed.aau5758.

Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer.

Author information

1
Department of Physiology, University of Melbourne, Melbourne, VIC 3010, Australia. matt.watt@unimelb.edu.au renea.taylor@monash.edu.
2
Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity, Department of Physiology, Monash University, Clayton, VIC 3800, Australia.
3
Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Physiology, Monash University, Clayton, VIC 3800, Australia.
4
Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC 3800, Australia.
5
Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men's Health, Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
6
Department of Physiology, University of Melbourne, Melbourne, VIC 3010, Australia.
7
Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4GJ, UK.
8
Monash Biomedical Proteomics Facility and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
9
Departments of Chemistry, Molecular and Cell Biology, and Nutritional Sciences and Toxicology, University of California, Berkley, Berkeley, CA, USA.
10
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia.
11
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia.
12
TissuPath, Mount Waverley, VIC 3149, Australia.
13
Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2R7, Canada.
14
Department of Surgery, Faculty of Medicine, Monash University, Clayton, VIC 3800, Australia.
15
Monash Partners Comprehensive Cancer Consortium, Monash Biomedicine Discovery Institute Cancer Program, Prostate Cancer Research Group, Department of Physiology, Monash University, Clayton, VIC 3800, Australia. matt.watt@unimelb.edu.au renea.taylor@monash.edu.

Abstract

Metabolism alterations are hallmarks of cancer, but the involvement of lipid metabolism in disease progression is unclear. We investigated the role of lipid metabolism in prostate cancer using tissue from patients with prostate cancer and patient-derived xenograft mouse models. We showed that fatty acid uptake was increased in human prostate cancer and that these fatty acids were directed toward biomass production. These changes were mediated, at least partly, by the fatty acid transporter CD36, which was associated with aggressive disease. Deleting Cd36 in the prostate of cancer-susceptible Pten-/- mice reduced fatty acid uptake and the abundance of oncogenic signaling lipids and slowed cancer progression. Moreover, CD36 antibody therapy reduced cancer severity in patient-derived xenografts. We further demonstrated cross-talk between fatty acid uptake and de novo lipogenesis and found that dual targeting of these pathways more potently inhibited proliferation of human cancer-derived organoids compared to the single treatments. These findings identify a critical role for CD36-mediated fatty acid uptake in prostate cancer and suggest that targeting fatty acid uptake might be an effective strategy for treating prostate cancer.

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