Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer
Authors
Watt, Matthew JClark, Ashlee K
Selth, Luke A
Haynes, Vanessa R
Lister, Natalie
Rebello, Richard
Porter, Laura H
Niranjan, Birunthi
Whitby, Sarah T
Lo, Jennifer
Huang, Cheng
Schittenhelm, Ralf B
Anderson, Kimberley E
Furic, Luc
Wijayaratne, Poornima R
Matzaris, Maria
Montgomery, Magdalene K
Papargiris, Melissa
Norden, Sam
Febbraio, Maria
Risbridger, Gail P
Frydenberg, Mark
Nomura, Daniel K
Taylor, Renea A
Affiliation
Department of Physiology, University of Melbourne, Melbourne, VIC 3010, AustraliaIssue Date
2019
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Show full item recordAbstract
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.Citation
Watt MJ, Clark AK, Selth LA, Haynes VR, Lister N, Rebello R, et al. Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer. Sci Transl Med. 2019 Feb 6;11(478).Journal
Science Translational MedicineDOI
10.1126/scitranslmed.aau5758PubMed ID
30728288Additional Links
https://dx.doi.org/10.1126/scitranslmed.aau5758Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1126/scitranslmed.aau5758
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