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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Vydané v:Cancer cell Ročník 27; číslo 1; s. 57
Hlavní autori: 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
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 12.01.2015
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ISSN:1878-3686, 1878-3686
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Shrnutí: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.
Bibliografia:ObjectType-Article-1
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content type line 23
ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccell.2014.12.002