Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids
Open accessAbstract
Cancer cell growth requires fatty acids to replicate cellular membranes. The kinase Akt is known to up-regulate fatty acid synthesis and desaturation, which is carried out by the oxygen-consuming enzyme stearoyl-CoA desaturase (SCD)1. We used (13)C tracers and lipidomics to probe fatty acid metabolism, including desaturation, as a function of oncogene expression and oxygen availability. During hypoxia, flux from glucose to acetyl-CoA decreases, and the fractional contribution of glutamine to fatty acid synthesis increases. In addition, we find that hypoxic cells bypass de novo lipogenesis, and thus, both the need for acetyl-CoA and the oxygen-dependent SCD1-reaction, by scavenging serum fatty acids. The preferred substrates for scavenging are phospholipids with one fatty acid tail (lysophospholipids). Hypoxic reprogramming of de novo lipogenesis can be reproduced in normoxic cells by Ras activation. This renders Ras-driven cells, both in culture and in allografts, resistant to SCD1 inhibition. Thus, a mechanism by which oncogenic Ras confers metabolic robustness is through lipid scavenging.
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Hypoxic cells import ready-made unsaturated fatty acids from the environment as lysophospholipids.
“hypoxic cells import “ready-made” unsaturated fatty acids from the surrounding environment in a form of single acyl chain-containing lysophospholipids”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Kamphorst et al., 2013
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- Authors
- Kamphorst, J. J., Cross, J. R., Fan, J., de Stanchina, E., Mathew, R., White, E. P., Thompson, C. B., & Rabinowitz, J. D.
- Affiliations
- Princeton University (US)
- Cancer Biology and Genetics Program and
- Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY 10065;
- Rutgers Cancer Institute (US)
- Rutgers, The State University of New Jersey (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-05-13
- Volume
- 110
- Issue
- 22
- Pages
- 8882-8887
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3670379
- OpenAlex
- W2015012139
- Cited by
- 726
- References
- 39
- Citations by year
- 2026: 26 · 2025: 49 · 2024: 60 · 2023: 58 · 2022: 77 · 2021: 71 · 2020: 58 · 2019: 65 · 2018: 59 · 2017: 56 · 2016: 65 · 2015: 46 · 2014: 27 · 2013: 9
- FWCI
- 17.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Hope Funds for Cancer Research
- National Cancer Institute (1R01CA16359-01A1, P30CA016359)
- National Institute of General Medical Sciences (P50GM071508)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- hypoxia, oncogenic Ras, lysophospholipids, stearoyl-CoA desaturase 1, fatty acid desaturation, de novo lipogenesis, Akt signaling, acetyl-CoA, cancer metabolism, metabolic reprogramming
- MeSH terms
- Animals, Autophagy, Carbon Isotopes, Fatty Acids, Glucose, Glutamine, Humans, Neoplasms, Oxygen Consumption, Phospholipids, Pinocytosis, Stearoyl-CoA Desaturase, Cell Hypoxia, Mice, Knockout, ras Proteins, Cell Line, Tumor, Cell Proliferation, Lipogenesis, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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