The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Triglycerides Promote Lipid Homeostasis during Hypoxic Stress by Balancing Fatty Acid Saturation
Open accessAbstract
Lipid droplets, which store triglycerides and cholesterol esters, are a prominent feature of clear cell renal cell carcinoma (ccRCC). Although their presence in ccRCC is critical for sustained tumorigenesis, their contribution to lipid homeostasis and tumor cell viability is incompletely understood. Here we show that disrupting triglyceride synthesis compromises the growth of both ccRCC tumors and ccRCC cells exposed to tumor-like conditions. Functionally, hypoxia leads to increased fatty acid saturation through inhibition of the oxygen-dependent stearoyl-CoA desaturase (SCD) enzyme. Triglycerides counter a toxic buildup of saturated lipids, primarily by releasing the unsaturated fatty acid oleate (the principal product of SCD activity) from lipid droplets into phospholipid pools. Disrupting this process derails lipid homeostasis, causing overproduction of toxic saturated ceramides and acyl-carnitines as well as activation of the NF-κB transcription factor. Our work demonstrates that triglycerides promote homeostasis by "buffering" specific fatty acids.
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Cites
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Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis
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BackgroundMacropinocytosis of protein is an amino acid supply route in Ras-transformed cells
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Self-citationPancreatic cancers require autophagy for tumor growth
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Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis
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HIF drives lipid deposition and cancer in ccRCC via repression of fatty acid metabolism
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Cited by
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612
The hallmarks of cancer metabolism: still emerging
Pavlova, N. N., Zhu, J., & Thompson, C. B. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.01.007 · Cited by 1,418
Cellular Adaptation to Hypoxia through Hypoxia Inducible Factors and beyond
Lee, P., Chandel, N. S., & Simon, M. C. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0227-y · Cited by 1,272
Self-citationMetabolic regulation of cell growth and proliferation
Zhu, J., & Thompson, C. B. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0123-5 · Cited by 1,116
Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
Snaebjornsson, M. T., Janaki-Raman, S., & Schulze, A. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.010 · Cited by 1,097
Metadata
- Authors
- Ackerman, D., Tumanov, S., Qiu, B., Michalopoulou, E., Spata, M., Azzam, A., Xie, H., Simon, M. C., & Kamphorst, J. J.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 24
- Issue
- 10
- Pages
- 2596-2605.e5
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2891967018
- Cited by
- 305
- References
- 10
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- gold
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