Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress

Zachary T. Schug(Cancer Research UK), Barrie Peck(The Honourable Society of Lincoln's Inn), Dylan T. Jones(John Radcliffe Hospital), Qifeng Zhang(Babraham Institute), Shaun Grosskurth(AstraZeneca (United Kingdom)), Israt S. Alam(Hammersmith Hospital), Louise Goodwin(AstraZeneca (United Kingdom)), Elizabeth A. Smethurst(Babraham Institute), Susan Mason(Cancer Research UK), Karen Blyth(Cancer Research UK), Lynn McGarry(Cancer Research UK), Daniel James(Cancer Research UK), Emma Shanks(Cancer Research UK), Gabriela Kalna(Cancer Research UK), Rebecca E. Saunders(The Honourable Society of Lincoln's Inn), Ming Jiang(The Honourable Society of Lincoln's Inn), Michael Howell(The Honourable Society of Lincoln's Inn), François Lassailly(The Honourable Society of Lincoln's Inn), May Zaw Thin(The Honourable Society of Lincoln's Inn), Bradley Spencer‐Dene(The Honourable Society of Lincoln's Inn), Gordon Stamp(The Honourable Society of Lincoln's Inn), Niels J. F. van den Broek(Cancer Research UK), Gillian Mackay(Cancer Research UK), Vinay Bulusu(University of Glasgow), Jurre J. Kamphorst(University of Glasgow), Saverio Tardito(Cancer Research UK), David Strachan(Cancer Research UK), Adrian L. Harris(John Radcliffe Hospital), Eric O. Aboagye(Hammersmith Hospital), Susan E. Critchlow(AstraZeneca (United Kingdom)), Michael J.O. Wakelam(Babraham Institute), Almut Schulze(The Honourable Society of Lincoln's Inn), Eyal Gottlieb(Cancer Research UK)
Cancer Cell
January 1, 2015
10.1016/j.ccell.2014.12.002
Cited by 813Open Access
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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.

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