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

MJ Watt; AK Clark; LA Selth; VR Haynes; N Lister; R Rebello; LH Porter; B Niranjan; ST Whitby; J Lo; C Huang; RB Schittenhelm; KE Anderson; L Furic; PR Wijayaratne; M Matzaris; MK Montgomery; M Papargiris; S Norden; M Febbraio; GP Risbridger; M Frydenberg; DK Nomura; RA Taylor

Journal article

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

MJ Watt, AK Clark, LA Selth, VR Haynes, N Lister, R Rebello, LH Porter, B Niranjan, ST Whitby, J Lo, C Huang, RB Schittenhelm, KE Anderson, L Furic, PR Wijayaratne, M Matzaris, MK Montgomery, M Papargiris, S Norden, M Febbraio Show all

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2019

DOI: 10.1126/scitranslmed.aau5758

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 ca..

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University of Melbourne Researchers

Matt Watt Author

Richard Rebello Author

Magda Montgomery Author

Renea Taylor Author

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Grants

Awarded by Prostate Cancer Foundation of Australia

Awarded by National Health and Medical Research Council of Australia

Awarded by Victorian Cancer Agency

Awarded by Department of Health and Human Services acting through the Victorian Cancer Agency

Funding Acknowledgements

This work was supported by the Prostate Cancer Foundation of Australia (ID: PCFA-NCG 3313, awarded to M.J.W. and R.A.T.) and the Diabetes Australia Research Trust (awarded to M.J.W.). M.J.W., M.K.M., L.A.S., and G.P.R. are supported by the National Health and Medical Research Council of Australia (APP1077703, APP1143224, APP1102752, and APP1121057), and R.A.T. is supported by the Victorian Cancer Agency (MCRF15023). L.F. is supported by the Department of Health and Human Services acting through the Victorian Cancer Agency (MCRF16007).