The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments
Open accessAbstract
BACKGROUND: Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid biosynthesis has been predicted to be an essential process in cancer cells. However, it is unclear which enzymes within this pathway offer the best selectivity for cancer cells and could be suitable therapeutic targets. RESULTS: Using functional genomics, we identified stearoyl-CoA desaturase (SCD), an enzyme that controls synthesis of unsaturated fatty acids, as essential in breast and prostate cancer cells. SCD inhibition altered cellular lipid composition and impeded cell viability in the absence of exogenous lipids. SCD inhibition also altered cardiolipin composition, leading to the release of cytochrome C and induction of apoptosis. Furthermore, SCD was required for the generation of poly-unsaturated lipids in cancer cells grown in spheroid cultures, which resemble those found in tumour tissue. We also found that SCD mRNA and protein expression is elevated in human breast cancers and predicts poor survival in high-grade tumours. Finally, silencing of SCD in prostate orthografts efficiently blocked tumour growth and significantly increased animal survival. CONCLUSIONS: Our data implicate lipid desaturation as an essential process for cancer cell survival and suggest that targeting SCD could efficiently limit tumour expansion, especially under the metabolically compromised conditions of the tumour microenvironment.
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Cites
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Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation
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“Discussion Increased lipid biosynthesis is an important feature of cancer cells [6, 7, 29].”
Cellular Fatty Acid Metabolism and Cancer
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Self-citationHypoxia, HIF1 and glucose metabolism in the solid tumour
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Fatty acid synthesis: a potential selective target for antineoplastic therapy
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“While most normal adult tissues use dietary lipids provided by the blood stream, many cancers show increased rates of de novo fatty acid (FA) biosynthesis [8].”
Mera, P., Bentebibel, A., López-Viñas, E., Cordente, A. G., Gurunathan, C., Sebastián, D., Vázquez, I., Herrero, L., Ariza, X., Gómez-Puertas, P., et al. (2009) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.11.020 · Cited by 57
Cited by
The multifaceted roles of fatty acid synthesis in cancer
Röhrig, F., & Schulze, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.89 · Cited by 1,651
Self-citationReprogramming of fatty acid metabolism in cancer
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Targeting cancer metabolism in the era of precision oncology
Stine, Z. E., Schug, Z. T., Salvino, J. M., & Dang, C. V. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00339-6 · Cited by 1,189
Self-citationGreasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
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Self-citationLipid metabolism reprogramming and its potential targets in cancer
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Metadata
- Authors
- Peck, B., Schug, Z. T., Zhang, Q., Dankworth, B., Jones, D. T., Smethurst, E., Patel, R., Mason, S., Jiang, M., Saunders, R., Howell, M., Mitter, R., Spencer-Dene, B., Stamp, G., McGarry, L., James, D., Shanks, E., Aboagye, E. O., Critchlow, S. E., Leung, H. Y., Harris, A. L., Wakelam, M. J. O., Gottlieb, E., & Schulze, A.
- Venue
- Cancer & Metabolism
- Published
- 2016-04-01
- Volume
- 4
- Issue
- 1
- Pages
- 6-6
- ISSN
- 2049-3002 (ISSN-L)
- OpenAlex
- W2314067388
- Cited by
- 254
- References
- 10
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- gold
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- Peck, B., Schug, Z. T., Zhang, Q., Dankworth, B., Jones, D. T., Smethurst, E., Patel, R., Mason, S., Jiang, M., Saunders, R., Howell, M., Mitter, R., Spencer-Dene, B., Stamp, G., McGarry, L., James, D., Shanks, E., Aboagye, E. O., Critchlow, S. E., . . . Schulze, A. (2016). Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments. Cancer & Metabolism. https://doi.org/10.1186/s40170-016-0146-8
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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