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

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 FebbraioGail P. Risbridger, Mark Frydenberg, Daniel K. Nomura, Renea A. Taylor

Research output: Contribution to journalArticlepeer-review

152 Citations (Scopus)


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.

Original languageEnglish
Article numbereaau5758
Number of pages12
JournalScience Translational Medicine
Issue number478
Publication statusPublished - 6 Feb 2019
Externally publishedYes


  • Prostate cancer
  • cancer metabolism
  • fatty acid translocase CD36
  • treating prostate cancer


Dive into the research topics of 'Suppressing fatty acid uptake has therapeutic effects in preclinical models of prostate cancer'. Together they form a unique fingerprint.

Cite this