Journal article
ELOVL5 is a critical and targetable fatty acid elongase in prostate cancer
MM Centenera, JS Scott, J Machiels, ZD Nassar, DC Miller, I Zinonos, J Dehairs, IJG Burvenich, G Zadra, PM Chetta, C Bango, E Evergren, NK Ryan, JL Gillis, CY Mah, T Tieu, AR Hanson, R Carelli, K Bloch, V Panagopoulos Show all
Cancer Research | Published : 2021
Abstract
The androgen receptor (AR) is the key oncogenic driver of prostate cancer, and despite implementation of novel AR targeting therapies, outcomes for metastatic disease remain dismal. There is an urgent need to better understand androgen-regulated cellular processes to more effectively target the AR dependence of prostate cancer cells through new therapeutic vulnerabilities. Transcriptomic studies have consistently identified lipid metabolism as a hallmark of enhanced AR signaling in prostate cancer, yet the relationship between AR and the lipidome remains undefined. Using mass spectrometry-based lipidomics, this study reveals increased fatty acyl chain length in phospholipids from prostate ca..
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Awarded by Australian Government
Funding Acknowledgements
The authors thank the study participants, urologists, nurses, histopathologists, and the South Australian Coordinator of the Australian Prostate Cancer Bioresource; Jessica Savage, who assisted in the recruitment and collection of patient material and information; Swati Irani for assistance with explant tissue culture and analysis; Dr. Ying Huang for immunostaining the tissue microarrays; the University of Adelaide Microscopy facility for technical assistance with electron microscopy. The authors acknowledge financial support from the Movember Foundation and Prostate Cancer Foundation of Australia (MRTA3 to L.M. Butler, J.V. Swinnen, W.D. Tilley, A.M. Scott, L.A. Selth, M.M. Centenera; MRTA1 to E.D. Williams), Prostate Cancer Foundation of Australia (NDDA2711 to L.M. Butler, M.M. Centenera, J.V. Swinnen; NCG1816 to L.M. Butler, A. Cifuentes-Rius, N.H. Voelcker), the Research Foundation-Flanders (FWO G.0841.15 to J.V. Swinnen), the Stichting tegen Kanker (to J.V. Swinnen), KU Leuven (C16/15/073 and C32/17/052 to J.V. Swinnen), Interreg V-A (EMR23 to J.V. Swinnen and E. Waelkens), the National Health and Medical Research Council (1121057 to W.D. Tilley and L.A. Selth), the National Institute of Health (RO1CA131945 to M. Loda), the NCI (P50CA211024 to M. Loda), the Prostate Cancer Foundation (to M. Loda), the United States Department of Defense (PC150263 to G. Zadra; PC160357 to M. Loda; PC180582 to M. Loda, L.M. Butler, J.V. Swinnen), and the Dana-Farber Cancer Institute (Claudia Adams Barr Award in Innovative Basic Cancer Research to G. Zadra). M.M. Centenera was supported by a Prostate Cancer Foundation of Australia Young Investigator Award (YIG0412). Z.D. Nassar was supported by National Health and Medical Research Center Early Career Fellowship (1138648) and Prostate Cancer Foundation of Australia John Mills Young Investigator Award (YI1417). T. Tieu and N.H. Voelcker acknowledge support from the Office of the Chief Executive and CSIRO Manufacturing. T. Tieu acknowledges support of an Australian Government RTP scholarship. A. Cifuentes-Rius was supported by a National Health and Medical Research Council Early Career Fellowship (1112432). L.M. Butler was supported by an ARC Future Fellowship (130101004). L.M. Butler and L.A. Selth are supported by Principal Cancer Research Fellowships awarded by Cancer Council's Beat Cancer project on behalf of its donors, the state government through the Department of Health, and the Australian Government through the Medical Research Future Fund (PRF1117 and PRF2919).