title: Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress.
abstract: A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment.
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Schug
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Barrie
authors.initials: B
authors.lastname: Peck
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: Qifeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: Shaun
authors.initials: S
authors.lastname: Grosskurth
authors.affiliation: Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Israt S
authors.initials: IS
authors.lastname: Alam
authors.affiliation: AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Goodwin
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, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Mason
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Blyth
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: McGarry
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: James
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Shanks
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kalna
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Saunders
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Howell
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Francois
authors.initials: F
authors.lastname: Lassailly
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: May Zaw
authors.initials: MZ
authors.lastname: Thin
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Bradley
authors.initials: B
authors.lastname: Spencer-Dene
authors.affiliation: Cancer Research UK, London Institute, 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, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Niels J F
authors.initials: NJ
authors.lastname: van den Broek
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Mackay
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Vinay
authors.initials: V
authors.lastname: Bulusu
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Jurre J
authors.initials: JJ
authors.lastname: Kamphorst
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: Saverio
authors.initials: S
authors.lastname: Tardito
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Strachan
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: 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: Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Michael J O
authors.initials: MJ
authors.lastname: Wakelam
authors.affiliation: Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Almut
authors.initials: A
authors.lastname: Schulze
authors.affiliation: Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: e.gottlieb@beatson.gla.ac.uk.
authors.forename: Eyal
authors.initials: E
authors.lastname: Gottlieb
mesh_terms: D000106:Acetate-CoA Ligase / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005227:Fatty Acids / Q000378:metabolism*; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013312:Stress, Physiological
chemical_list: D005227:Fatty Acids; C000595379:ACSS2 protein, human; C000595378:ACSS2 protein, mouse; D000106:Acetate-CoA Ligase