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Updated: Jul 12, 2025
07:20
Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
Published on: January 31, 2025
516
Sigma1 Regulates Lipid Droplet-mediated Redox Homeostasis Required for Prostate Cancer Proliferation
Halley M Oyer1,2, Alexandra R Steck1,2, Charles G Longen1,2
1Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Cancer Research Communications
|October 24, 2023
Summary
Targeting Sigma1 protein disrupts lipid droplet homeostasis in prostate cancer, inhibiting proliferation and tumor growth by preventing reactive oxygen species sequestration.
Area of Science:
- Cell Biology
- Cancer Metabolism
- Redox Homeostasis
Background:
- Lipid droplets (LDs) are key metabolic organelles involved in cellular processes.
- In prostate cancer, LD accumulation correlates with aggressiveness and poor outcomes.
- Androgen receptor (AR) signaling drives prostate cancer by regulating LDs, autophagy, and oxidative stress.
Purpose of the Study:
- To investigate the role of Sigma1/SIGMAR1 in regulating lipid droplet metabolism in prostate cancer.
- To elucidate how Sigma1 inhibition affects cellular redox homeostasis and proliferation.
Main Methods:
- Investigated Sigma1's role in prostate cancer cell lines.
- Assessed the impact of Sigma1 inhibition on lipophagy, reactive oxygen species (ROS) levels, and cell proliferation.
- Correlated SIGMAR1 transcript levels with lipid metabolism and ROS pathways in prostate tumors.
Main Results:
- Sigma1 inhibition triggered lipophagy, an LD-selective autophagy, preventing LD accumulation.
- This disruption impaired the sequestration of reactive oxygen species (ROS), leading to suppressed cell proliferation in vitro.
- Tumor growth was significantly inhibited in vivo following Sigma1 targeting.
- SIGMAR1 transcript levels were strongly associated with lipid metabolism and ROS pathways in prostate tumors.
Conclusions:
- Sigma1 regulates lipid droplet metabolism and redox homeostasis in prostate cancer.
- Targeting Sigma1 disrupts the metabolic adaptations supporting cancer cell proliferation.
- Sigma1 represents a novel, pharmacologically targetable vulnerability in prostate cancer.
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