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Type: Journal article
Title: Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer
Author: Watt, M.J.
Clark, A.K.
Selth, L.A.
Haynes, V.R.
Lister, N.
Rebello, R.
Porter, L.H.
Niranjan, B.
Whitby, S.T.
Lo, J.
Huang, C.
Schittenhelm, R.B.
Anderson, K.E.
Furic, L.
Wijayaratne, P.R.
Matzaris, M.
Montgomery, M.K.
Papargiris, M.
Norden, S.
Febbraio, M.
et al.
Citation: Science Translational Medicine, 2019; 11(478):1-12
Publisher: American Association for the Advancement of Science
Issue Date: 2019
ISSN: 1946-6234
Statement of
Matthew J. Watt, Ashlee K. Clark, Luke A. Selth, Vanessa R. Haynes, Natalie Lister, Richard Rebello, Laura H. Porter, Birunthi Niranjan, Sarah T. Whitby, Jennifer Lo, Cheng Huang, Ralf B. Schittenhelm, Kimberley E. Anderson, Luc Furic, Poornima R. Wijayaratne, Maria Matzaris, Magdalene K. Montgomery, Melissa Papargiris, Sam Norden, Maria Febbraio, Gail P. Risbridger, Mark Frydenberg, Daniel K. Nomura, Renea A. Taylor
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.
Keywords: Prostate
Cell Line, Tumor
Epithelial Cells
Prostatic Neoplasms
Neoplasm Invasiveness
Disease Models, Animal
Disease Progression
Fatty Acids
RNA, Small Interfering
Antibodies, Monoclonal
Tumor Burden
Gene Silencing
Gene Deletion
Lipid Metabolism
PTEN Phosphohydrolase
CD36 Antigens
Rights: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works is an article distributed under the terms of the Science Journals Default License.
DOI: 10.1126/scitranslmed.aau5758
Grant ID:
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