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

Schug, Z. T. et al. (2015) Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress. Cancer Cell, 27(1), pp. 57-71. (doi:10.1016/j.ccell.2014.12.002) (PMID:25584894) (PMCID:PMC4297291)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Strachan, Mr David and Bulusu, Dr Vinay and Tardito, Mr Saverio and Schug, Dr Zachary and James, Mr Daniel and McGarry, Ms Lynn and Kalna, Dr Gabriela and Shanks, Dr Emma and Blyth, Dr Karen and Gottlieb, Professor Eyal and Mason, Miss Susan and Mackay, Dr Gillian and Kamphorst, Dr Jurre
Authors: Schug, Z. T., Peck, B., Jones, D. T., Zhang, Q., Grosskurth, S., Alam, I. S., Goodwin, L. M., Smethurst, E., Mason, S., Blyth, K., McGarry, L., James, D., Shanks, E., Kalna, G., Saunders, R. E., Jiang, M., Howell, M., Lassailly, F., Thin, M. Z., Spencer-Dene, B., Stamp, G., van den Broek, N. J.F., Mackay, G., Bulusu, V., Kamphorst, J. J., Tardito, S., Strachan, D., Harris, A. L., Aboagye, E. O., Critchlow, S. E., Wakelam, M. J.O., Schulze, A., and Gottlieb, E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Cancer Cell
Publisher:Elsevier (Cell Press)
ISSN:1535-6108
ISSN (Online):1878-3686
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Cancer Cell 27(1):57-71
Publisher Policy:Reproduced under a Creative Commons License

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