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

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    Authors
    Watt, Matthew J
    Clark, 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
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    Affiliation
    Department of Physiology, University of Melbourne, Melbourne, VIC 3010, Australia
    Issue Date
    2019
    
    Metadata
    Show full item record
    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.
    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 Medicine
    URI
    http://hdl.handle.net/10541/621989
    DOI
    10.1126/scitranslmed.aau5758
    PubMed ID
    30728288
    Additional Links
    https://dx.doi.org/10.1126/scitranslmed.aau5758
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1126/scitranslmed.aau5758
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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