Lipid Metabolism Dynamics in Prostate Cancer

Lipid metabolism in prostate cancer encompasses the coordinated regulation of lipid synthesis, uptake, storage and oxidation to support tumour growth, survival and therapy resistance. Androgen receptor signalling and transcription factors such as SREBF1 drive de novo lipogenesis and enhanced fatty acid uptake, supplying precursors for membrane biogenesis and energy. Intracellular lipid droplets serve as dynamic reservoirs that buffer metabolic stress and facilitate rapid proliferation under nutrient limitation. Concurrently, upregulated β-oxidation generates ATP and reducing equivalents, aiding survival in hypoxic or glucose-deprived niches. Alterations in the balance of saturated and unsaturated phospholipids modulate membrane fluidity and redox homeostasis, influencing sensitivity to ferroptosis. Moreover, interactions with adipocytes in the bone marrow microenvironment further reprogramme tumour lipid utilisation. These interconnected pathways contribute to endocrine and chemotherapeutic resistance, highlighting lipid metabolism as a promising target for dietary, pharmacological and combination strategies to improve clinical outcomes.

Research from Nature Portfolio

Recent studies have identified mitochondrial 2,4-dienoyl-CoA reductase (DECR1) as a pivotal factor in castration-resistant prostate cancer, where it regulates an auxiliary lipid β-oxidation pathway. DECR1 maintains redox balance by controlling the ratio of saturated to unsaturated phospholipids; its loss induces endoplasmic reticulum stress, sensitises cells to ferroptosis and impairs tumour growth in vivo. A foundational investigation has also revealed that a high-fat diet remodels the systemic metabolome to amplify the MYC oncogenic programme. Saturated fat intake promotes specific histone hypomethylation at MYC-target promoters, driving cellular proliferation and tumour burden—effects that can be reversed by dietary modification.

Lipid Metabolism Dynamics in Prostate Cancer publication trend

The graph below shows the total number of articles in lipid metabolism dynamics in prostate cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Fatty acid oxidation (FAO): Mitochondrial and peroxisomal pathway converting long-chain fatty acids into acetyl-CoA for ATP generation.

Lipid droplets (LDs): Intracellular organelles storing neutral lipids, serving as energy reserves and stress buffers.

β-Oxidation: Sequential enzymatic degradation of acyl-CoA molecules into acetyl-CoA units.

Ferroptosis: Iron-dependent regulated cell death driven by uncontrolled lipid peroxidation.

Peroxisome proliferator-activated receptor α (PPARα): Nuclear receptor that controls genes involved in fatty acid transport and oxidation.

Carnitine palmitoyltransferase 1A (CPT1A): Mitochondrial enzyme facilitating entry of long-chain fatty acids into the matrix for β-oxidation.

Reactive oxygen species (ROS): Chemically reactive oxygen species that can induce oxidative damage or act as signalling molecules.

SREBF1: Sterol regulatory element-binding transcription factor 1, a master regulator of cholesterol and fatty acid biosynthesis.

References

1. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nature Communications (2020).
2. High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program. Nature Communications (2019).
3. PIM1 drives lipid droplet accumulation to promote proliferation and survival in prostate cancer. Oncogene (2023).
4. SREBF1-based metabolic reprogramming in prostate cancer promotes tumor ferroptosis resistance. Cell Death Discovery (2025).
5. Bone marrow adipocytes promote the warburg phenotype in metastatic prostate tumors via HIF-1α activation. Oncotarget (2016).