Journal
NATURE
Volume 566, Issue 7744, Pages 403-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-0904-1
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Funding
- VIB International PhD student fellowship
- Kom op tegen Kanker
- FWO fellowships
- CPRIT [RP160089]
- National Cancer Institute [R35CA22044901]
- German Cancer Aid [DKH-111886, DKH-70112257]
- LMUexcellent
- Bettina-Brau-Stiftung
- Dr. Leopold und Carmen Ellinger Foundation
- Matthias-Lackas Foundation
- Walter Schulz Foundation
- Wilhelm Sander Foundation [2016.167.1]
- Gert & Susanna Mayer Foundation
- Deutsche Forschungsgemeinschaft [DFG 391665916]
- European Research Council under the ERC Consolidator Grant [771486-MetaRegulation]
- European Research Council under Marie Curie CIG [617727-MetabolismConnect]
- FWO Odysseus II
- KU Leuven Methusalem Co-funding
- Bayer AG
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Most tumours have an aberrantly activated lipid metabolism(1,2) that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation(3). This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.
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