Journal
CELL REPORTS
Volume 34, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.108738
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Funding
- Movember Foundation
- Prostate Cancer Foundation of Australia
- Australian Government Department of Health through a Movember Revolutionary Team Award
- Australian Government
- Science and Engineering Faculty (QUT, Brisbane, Australia)
- Australian Research Council [DP150101715, LP180100238, DP190101486]
- Australian Government RTP scholarship
- Interreg V EMR
- Netherlands Ministry of Economic Affairs within the ``EURLIPIDS'' project [EMR23]
- Australian Research Council [LP180100238] Funding Source: Australian Research Council
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Canonical fatty acid metabolism describes specific enzyme-substrate interactions resulting in well-defined products. Profiling of lipids in prostate cancer cell lines revealed unusual unsaturated fatty acids not described by canonical pathways. Direct desaturation of fatty acids by FADS2 generated new unsaturated fatty acid families rarely reported in human-derived cells, with functional roles in membrane structure and signaling.
Canonical fatty acid metabolism describes specific enzyme-substrate interactions that result in products with well-defined chain lengths, degree(s), and positions of unsaturation. Deep profiling of lipids across a range of prostate cancer cell lines reveals a variety of fatty acids with unusual site(s) of unsaturation that are not described by canonical pathways. The structure and abundance of these unusual lipids correlate with changes in desaturase expression and are strong indicators of cellular phenotype. Gene silencing and stable isotope tracing demonstrate that direct Delta 6 and Delta 8 desaturation of 14:0 (myristic), 16:0 (palmitic), and 18:0 (stearic) acids by FADS2 generate new families of unsaturated fatty acids (including n-8, n-10, and n-12) that have rarely-if ever-been reported in human-derived cells. Isomer-resolved lipidomics reveals the selective incorporation of these unusual fatty acids into complex structural lipids and identifies their presence in cancer tissues, indicating functional roles in membrane structure and signaling.
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