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Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments

Please always quote using this URN: urn:nbn:de:bvb:20-opus-145905
  • 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 alteredBackground 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.show moreshow less

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Author: Barrie Peck, Zachary T. Schug, Qifeng Zhang, Beatrice Dankworth, Dylan T. Jones, Elizabeth Smethurst, Rachana Patel, Susan Mason, Ming Jian, Rebecca Saunders, Michael Howell, Richard Mitter, Bradley Spencer-Dene, Gordon Stamp, Lynn McGarry, Daniel James, Emma Shanks, Eric O. Aboagye, Susan E. Critchlow, Hing Y. Leung, Adrian L. Harris, Michael J. O. Wakelam, Eyal Gottlieb, Almut Schulze
URN:urn:nbn:de:bvb:20-opus-145905
Document Type:Journal article
Faculties:Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Cancer & Metabolism
Year of Completion:2016
Volume:4
Issue:6
Source:Cancer & Metabolism (2016) 4:6 DOI 10.1186/s40170-016-0146-8
DOI:https://doi.org/10.1186/s40170-016-0146-8
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:SCD; breast cancer; lipid desaturation; lipidomics; prostate cancer
Release Date:2017/03/30
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2016
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung