Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis.

ELife
Z. D. NassarLisa M Butler

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.

References

May 1, 1990·The Journal of Clinical Investigation·C R RoeR McVie
Oct 1, 1990·The American Journal of Clinical Nutrition·M L SlatteryT K French
Apr 13, 2000·Biochimica Et Biophysica Acta·J K Hiltunen, Y Qin
Feb 22, 2002·International Journal of Cancer. Journal International Du Cancer·Johannes V SwinnenGuido Verhoeven
Jan 27, 2005·Lipids·Nadia M Attar-BashiAndrew J Sinclair
Aug 12, 2005·The Journal of Urology·Dean OrnishPeter R Carroll
Sep 20, 2005·Molecular Genetics and Metabolism·Lara R NymanPhilip A Wood
Nov 23, 2005·Urologic Oncology·Janet Laura Colli, Albert Colli
May 10, 2006·Prostate Cancer and Prostatic Diseases·Y Liu
Dec 19, 2006·Nature Genetics·Scott A TomlinsArul M Chinnaiyan
Nov 21, 2007·Molecular Genetics and Metabolism·Shaonin JiPhilip A Wood
Feb 19, 2008·Journal of Lipid Research·Vitali MatyashDominik Schwudke
Sep 30, 2008·Cancer Causes & Control : CCC·Song-Yi ParkLaurence N Kolonel
Mar 7, 1927·The Journal of General Physiology·O WarburgE Negelein
Mar 18, 2010·BMC Medical Genomics·Andrea SbonerOve Andrén
Jun 29, 2010·Cancer Cell·Barry S TaylorWilliam L Gerald
Feb 2, 2011·Molecular Cancer Therapeutics·Nancy B KuemmerleWilliam B Kinlaw
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Jun 30, 2011·Endocrine-related Cancer·Changmeng Cai, Steven P Balk
Nov 1, 2011·Nature Medicine·Kristin M NiemanErnst Lengyel
May 11, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Margaret M CenteneraLisa M Butler
May 29, 2012·Cell·Scott J DixonBrent R Stockwell
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Jul 12, 2012·American Journal of Epidemiology·Mara M EpsteinOve Andrén
Aug 17, 2012·The New England Journal of Medicine·Howard I ScherUNKNOWN AFFIRM Investigators
Apr 9, 2013·Biochimica Et Biophysica Acta·Giorgia ZadraMassimo Loda
May 11, 2013·Nutrition and Cancer·Shruti A ApteLinda A Degraffenried
Jun 12, 2013·Nature Reviews. Urology·Margaret M CenteneraLisa M Butler
Oct 11, 2013·The Journal of Pathology·Daniel Nava RodriguesJohann S de Bono
Dec 18, 2013·Diabetes, Obesity & Metabolism·K R HaynieR L Mynatt

❮ Previous
Next ❯

Citations

Jan 28, 2021·Biology·Min Ji KimSung Eun Kim
Feb 11, 2021·Analytical and Bioanalytical Chemistry·Jacob X M TruongPaul J Trim
Jan 9, 2021·Cancer & Metabolism·Shilpa R NagarajanAndrew J Hoy
Jan 24, 2021·Cancer Research·Ali GhoochaniTanya Stoyanova
Nov 21, 2020·Cell Metabolism·Jiashuo Zheng, Marcus Conrad
May 21, 2021·Advanced Biology·Zhi LinDaolin Tang
Aug 14, 2021·Frontiers in Oncology·Natalia ScagliaGiorgia Zadra
Aug 22, 2021·Nature Reviews. Cancer·Andrew J HoyLisa M Butler
Jun 20, 2021·Cancer Research·Laura A Sena, Samuel R Denmeade

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE21032
GSE16560
GSE22606
GSE69249
GSE56288
GSE35988
GSE6099
GSE55064

Methods Mentioned

BETA
Assay
xenografts
immunoprecipitation
xenograft
transfection
flow cytometry
RNA-seq
biopsy
PCR
ChIP-seq

Software Mentioned

MultiQuant
GraphPad prism
R limma voom - eBayes pipeline
TraceFinder
GraphPad
Seahorse Wave
R metafor
Integrated Genome Browser ( IGV
REACTOME
StatsModels

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.