Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition
Abstract
Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the “lipidome” in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 06, 2021
- Source ID
- 10.1158/0008-5472.can-20-3863
Entities
People
- Andrew D. Vincent
- Chui Yan Mah
- David J. Lynn
- David Waltregny
- Etienne Waelkens
- Frank Vanderhoydonc
- James G Kench
- Jelle Machiels
- Johannes V. Swinnen
- Jonas Dehairs
- Jurgen Stahl
- Katarzyna Bloch
- Lisa G. Horvath
- Lisa M Butler
- Luke A. Selth
- Margaret M. Centenera
- Marten F. Snel
- Max Moldovan
- Muralidhararao Bagadi
- Paul J Trim
- Rajdeep Das
- Rita Derua
- Shadrack M. Mutuku
- Swati Irani
- Thomas Gevaert
- Wayne D Tilley
- Xander Spotbeen
- Zeyad D Nassar
Organizations
- Australian Cancer Research Foundation
- Cancer Australia
- EMBL Australia
- Flinders University
- Katholieke Universiteit Leuven
- Movember Foundation
- National Health and Medical Research Council
- Prostate Cancer Foundation of Australia
- Royal Prince Alfred Hospital
- UZ Leuven
- United States Department of Defense
- University of Adelaide