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Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis
Open accessAbstract
KRAS is one of the most commonly mutated oncogenes in human cancer. Mutant KRAS aberrantly regulates metabolic networks. However, the contribution of cellular metabolism to mutant KRAS tumorigenesis is not completely understood. We report that mutant KRAS regulates intracellular fatty acid metabolism through Acyl-coenzyme A (CoA) synthetase long-chain family member 3 (ACSL3), which converts fatty acids into fatty Acyl-CoA esters, the substrates for lipid synthesis and β-oxidation. ACSL3 suppression is associated with depletion of cellular ATP and causes the death of lung cancer cells. Furthermore, mutant KRAS promotes the cellular uptake, retention, accumulation, and β-oxidation of fatty acids in lung cancer cells in an ACSL3-dependent manner. Finally, ACSL3 is essential for mutant KRAS lung cancer tumorigenesis in vivo and is highly expressed in human lung cancer. Our data demonstrate that mutant KRAS reprograms lipid homeostasis, establishing a metabolic requirement that could be exploited for therapeutic gain.
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Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
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Lipid metabolism in cancer: New perspectives and emerging mechanisms
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Metadata
- Authors
- Padanad, M. S., Konstantinidou, G., Venkateswaran, N., Melegari, M., Rindhe, S., Mitsche, M., Yang, C., Batten, K., Huffman, K. E., Liu, J., Tang, X., Rodriguez-Canales, J., Kalhor, N., Shay, J. W., Minna, J. D., McDonald, J., Wistuba, I. I., DeBerardinis, R. J., & Scaglioni, P. P.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 16
- Issue
- 6
- Pages
- 1614-1628
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2480163530
- Cited by
- 301
- References
- 9
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Padanad, M. S., Konstantinidou, G., Venkateswaran, N., Melegari, M., Rindhe, S., Mitsche, M., Yang, C., Batten, K., Huffman, K. E., Liu, J., Tang, X., Rodriguez-Canales, J., Kalhor, N., Shay, J. W., Minna, J. D., McDonald, J., Wistuba, I. I., DeBerardinis, R. J., & Scaglioni, P. P. (2016). Fatty Acid Oxidation Mediated by Acyl-CoA Synthetase Long Chain 3 Is Required for Mutant KRAS Lung Tumorigenesis. Cell Reports. https://doi.org/10.1016/j.celrep.2016.07.009
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
