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Updated: Nov 18, 2025
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
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ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer
Margaret M Centenera1,2,3, Julia S Scott1,2,3, Jelle Machiels4
1University of Adelaide Medical School, Adelaide, SA, Australia.
Cancer Research
|February 6, 2021
Summary
Androgen receptor (AR) signaling in prostate cancer drives increased fatty acid chain length via ELOVL5, promoting tumor growth and metastasis. Targeting this lipid metabolism pathway offers a new therapeutic vulnerability for advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Metabolic Research
Background:
- Androgen receptor (AR) is a key driver in prostate cancer, but metastatic outcomes remain poor.
- Understanding AR-regulated cellular processes is crucial for developing new therapies.
- Lipid metabolism is a known hallmark of AR signaling, but its specific role is undefined.
Purpose of the Study:
- To define the relationship between AR signaling and the lipidome in prostate cancer.
- To investigate the role of fatty acid elongation in AR-driven prostate cancer.
- To identify novel therapeutic targets within AR-regulated metabolic pathways.
Main Methods:
- Mass spectrometry-based lipidomics to analyze lipid profiles.
- Investigated the induction of ELOVL fatty acid elongase 5 (ELOVL5) by AR.
- Assessed ELOVL5 expression in prostate cancer cells, xenografts, and clinical samples.
- Studied the effects of ELOVL5 depletion and cis-vaccenic acid supplementation.
Main Results:
- Prostate cancer cells exhibit increased phospholipid fatty acyl chain length, regulated by AR.
- AR directly induces ELOVL5, which is upregulated in prostate cancer.
- ELOVL5 depletion impairs mitochondrial function, increases reactive oxygen species, and suppresses tumor growth and metastasis.
- Supplementation with cis-vaccenic acid reversed the effects of ELOVL5 knockdown.
Conclusions:
- Phospholipid elongation via ELOVL5 is a protumorigenic, AR-regulated metabolic pathway in prostate cancer.
- ELOVL5 is critical for tumor growth, metastasis, and is a potential therapeutic target.
- Targeting lipid elongation presents a novel strategy for treating metastatic prostate cancer.
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