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

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-de...

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Published in:Cancer cell Vol. 27; no. 1; p. 57
Main Authors: Schug, Zachary T, Peck, Barrie, Jones, Dylan T, Zhang, Qifeng, Grosskurth, Shaun, Alam, Israt S, Goodwin, Louise M, Smethurst, Elizabeth, Mason, Susan, Blyth, Karen, McGarry, Lynn, James, Daniel, Shanks, Emma, Kalna, Gabriela, Saunders, Rebecca E, Jiang, Ming, Howell, Michael, Lassailly, Francois, Thin, May Zaw, Spencer-Dene, Bradley, Stamp, Gordon, van den Broek, Niels J F, Mackay, Gillian, Bulusu, Vinay, Kamphorst, Jurre J, Tardito, Saverio, Strachan, David, Harris, Adrian L, Aboagye, Eric O, Critchlow, Susan E, Wakelam, Michael J O, Schulze, Almut, Gottlieb, Eyal
Format: Journal Article
Language:English
Published: United States 12.01.2015
Subjects:
Acetate-CoA Ligase - genetics
Acetate-CoA Ligase - metabolism
Animals
Cell Line, Tumor
Cell Proliferation
Disease Progression
Fatty Acids - metabolism
Gene Dosage
Gene Expression Regulation, Neoplastic
Humans
Hypoxia
MCF-7 Cells
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Stress, Physiological
ISSN:1878-3686, 1878-3686
Online Access:Get more information
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Summary: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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ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccell.2014.12.002