title: Inhibition of fatty acid desaturation is detrimental to cancer cell survival in metabolically compromised environments.
abstract: 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.
authors.affiliation: Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY UK.|Present address: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB UK.
authors.forename: Barrie
authors.initials: B
authors.lastname: Peck
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Schug
authors.affiliation: Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT UK.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department for Biochemistry and Molecular Biology, Theodor-Boveri-Institute, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Dankworth
authors.affiliation: Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS UK.
authors.forename: Dylan T
authors.initials: DT
authors.lastname: Jones
authors.affiliation: Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smethurst
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Rachana
authors.initials: R
authors.lastname: Patel
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Mason
authors.affiliation: High Throughput Screening Facility, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: High Throughput Screening Facility, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Saunders
authors.affiliation: High Throughput Screening Facility, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Bioinformatics and Biostatistics Service, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Mitter
authors.affiliation: Experimental Histopathology, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Bradley
authors.initials: B
authors.lastname: Spencer-Dene
authors.affiliation: Experimental Histopathology, The Francis Crick Institute, Lincoln`s Inn Fields Laboratories, 44 Lincoln`s Inn Fields, London, WC2A 3LY UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Stamp
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: McGarry
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: James
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Shanks
authors.affiliation: Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN UK.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Aboagye
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield, SK10 4TG UK.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Critchlow
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Hing Y
authors.initials: HY
authors.lastname: Leung
authors.affiliation: Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS UK.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.affiliation: Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT UK.
authors.forename: Michael J O
authors.initials: MJO
authors.lastname: Wakelam
authors.affiliation: Cancer Research UK, Beatson Institute, Switchback Rd, Glasgow, G61 1BD UK.
authors.forename: Eyal
authors.initials: E
authors.lastname: Gottlieb
authors.affiliation: Gene Expression Analysis Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3LY UK.|Department for Biochemistry and Molecular Biology, Theodor-Boveri-Institute, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.|Comprehensive Cancer Center Mainfranken, Josef-Schneider-Str. 6, 97080 Würzburg, Germany.
authors.forename: Almut
authors.initials: A
authors.lastname: Schulze
keywords: Breast cancer; Lipid desaturation; Lipidomics; Prostate cancer; SCD