Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress.

Autor:	Schug ZT; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Peck B; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Jones DT; Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK., Zhang Q; Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK., Grosskurth S; AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK., Alam IS; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK., Goodwin LM; AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK., Smethurst E; Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK., Mason S; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Blyth K; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., McGarry L; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., James D; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Shanks E; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Kalna G; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Saunders RE; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Jiang M; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Howell M; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Lassailly F; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Thin MZ; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Spencer-Dene B; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Stamp G; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., van den Broek NJ; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Mackay G; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Bulusu V; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Kamphorst JJ; Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Tardito S; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Strachan D; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK., Harris AL; Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK., Aboagye EO; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK., Critchlow SE; AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK., Wakelam MJ; Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK., Schulze A; Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK., Gottlieb E; Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: e.gottlieb@beatson.gla.ac.uk.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2015 Jan 12; Vol. 27 (1), pp. 57-71.
DOI:	10.1016/j.ccell.2014.12.002
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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