Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/23863
Title: Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis.
Austin Authors: Nassar, Zeyad D;Mah, Chui Yan;Dehairs, Jonas;Burvenich, Ingrid J G;Irani, Swati;Centenera, Margaret M;Helm, Madison;Shrestha, Raj K;Moldovan, Max;Don, Anthony S;Holst, Jeff;Scott, Andrew M ;Horvath, Lisa G;Lynn, David J;Selth, Luke A;Hoy, Andrew J;Swinnen, Johannes V;Butler, Lisa M
Affiliation: Precision Medicine, South Australian Health and Medical Research Institute, Adelaide, Australia
Oncology, Chris O'Brien Lifehouse, Sydney, Australia
School of Medical Sciences, University of New South Wales, Sydney, Australia
Olivia Newton-John Cancer Research Institute
Charles Perkins Centre, University of Sydney, Sydney, Australia
Medicine, University of Adelaide, Adelaide, Australia
Oncology, KU Leuven, Leuven, Belgium
Issue Date: 20-Jul-2020
metadata.dc.date: 2020-07-20
Publication information: eLife 2020; 9: e54166
Abstract: Fatty acid β-oxidation (FAO) is the main bioenergetic pathway in human prostate cancer (PCa) and a promising novel therapeutic vulnerability. Here we demonstrate therapeutic efficacy of targeting FAO in clinical prostate tumors cultured ex vivo, and identify DECR1, encoding the rate-limiting enzyme for oxidation of polyunsaturated fatty acids (PUFAs), as robustly overexpressed in PCa tissues and associated with shorter relapse-free survival. DECR1 is a negatively-regulated androgen receptor (AR) target gene and, therefore, may promote PCa cell survival and resistance to AR targeting therapeutics. DECR1 knockdown selectively inhibited β-oxidation of PUFAs, inhibited proliferation and migration of PCa cells, including treatment resistant lines, and suppressed tumor cell proliferation and metastasis in mouse xenograft models. Mechanistically, targeting of DECR1 caused cellular accumulation of PUFAs, enhanced mitochondrial oxidative stress and lipid peroxidation, and induced ferroptosis. These findings implicate PUFA oxidation via DECR1 as an unexplored facet of FAO that promotes survival of PCa cells.
URI: http://ahro.austin.org.au/austinjspui/handle/1/23863
DOI: 10.7554/eLife.54166
ORCID: 0000-0002-7779-2697
0000-0002-8820-4037
0000-0003-2698-3220
PubMed URL: 32686647
Type: Journal Article
Subjects: cancer biology
human
mouse
Appears in Collections:Journal articles

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