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

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

  • Cancer Cell. 2015 Jan 12;27(1):57-71. doi: 10.1016/j.ccell.2014.12.002.
Zachary T Schug 1 Barrie Peck 2 Dylan T Jones 3 Qifeng Zhang 4 Shaun Grosskurth 5 Israt S Alam 6 Louise M Goodwin 5 Elizabeth Smethurst 4 Susan Mason 1 Karen Blyth 1 Lynn McGarry 1 Daniel James 1 Emma Shanks 1 Gabriela Kalna 1 Rebecca E Saunders 2 Ming Jiang 2 Michael Howell 2 Francois Lassailly 2 May Zaw Thin 2 Bradley Spencer-Dene 2 Gordon Stamp 2 Niels J F van den Broek 1 Gillian Mackay 1 Vinay Bulusu 7 Jurre J Kamphorst 7 Saverio Tardito 1 David Strachan 1 Adrian L Harris 3 Eric O Aboagye 6 Susan E Critchlow 5 Michael J O Wakelam 4 Almut Schulze 2 Eyal Gottlieb 8
Affiliations

Affiliations

  • 1 Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
  • 2 Cancer Research UK, London Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • 3 Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.
  • 4 Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • 5 AstraZeneca, Mereside, Alderley Park, Macclesfield SK10 4TG, UK.
  • 6 Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
  • 7 Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
  • 8 Cancer Research UK, Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK. Electronic address: e.gottlieb@beatson.gla.ac.uk.
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.

Figures
Products