Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stressMore about Open Access at the Crick
Authors listZachary T Schug Barrie Peck Dylan T Jones Qifeng Zhang Shaun Grosskurth Israt S Alam Louise M Goodwin Elizabeth Smethurst Susan Mason Karen Blyth Lynn McGarry Daniel James Emma Shanks Gabriela Kalna Rebecca E Saunders Ming Jiang Michael Howell Francois Lassailly May Zaw Thin Bradley Spencer-Dene Gordon Stamp Niels JF van den Broek Gillian Mackay Vinay Bulusu Jurre J Kamphorst Saverio Tardito David Strachan Adrian L Harris Eric O Aboagye Susan E Critchlow Michael JO Wakelam Almut Schulze Eyal Gottlieb
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.