Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids Journal Article
| Authors: | Kamphorst, J. J.; Cross, J. R.; Fan, J.; de Stanchina, E.; Mathew, R.; White, E. P.; Thompson, C. B.; Rabinowitz, J. D. |
| Article Title: | Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids |
| Abstract: | 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 13C 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. |
| Keywords: | nonhuman; animal cell; mouse; gene expression; cell growth; oxygen; hypoxia; oncogene; glucose; fatty acid; lipid metabolism; lipogenesis; synthesis; glutamine; cells; carbon 13; fatty acid metabolism; isotope tracing; acetyl coenzyme a; lysophospholipid; lipogenesis in cancer; unsaturated fatty acid; fatty acid desaturation; hypoxic cell; lipidomics; ras transformed cell |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 110 |
| Issue: | 22 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2013-05-28 |
| Start Page: | 8882 |
| End Page: | 8887 |
| Language: | English |
| DOI: | 10.1073/pnas.1307237110 |
| PROVIDER: | scopus |
| PMCID: | PMC3670379 |
| PUBMED: | 23671091 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 July 2013" - "CODEN: PNASA" - "Source: Scopus" |
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