Acetate dependence of tumors

Sarah A Comerford, Zhiguang Huang, Xinlin Du, Yun Wang, Ling Cai, Agnieszka Witkiewicz, Holly Walters, Mohammed N. Tantawy, Allie Fu, H. Charles Manning, Jay D Horton, Robert E Hammer, Steven L McKnight, Benjamin P Tu

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation, and the regulation of gene expression. Highly glycolytic or hypoxic tumors must produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions. Here, we show that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. Despite exhibiting no gross deficits in growth or development, adult mice lacking ACSS2 exhibit a significant reduction in tumor burden in two different models of hepatocellular carcinoma. ACSS2 is expressed in a large proportion of human tumors, and its activity is responsible for the majority of cellular acetate uptake into both lipids and histones. These observations may qualify ACSS2 as a targetable metabolic vulnerability of a wide spectrum of tumors.

Original languageEnglish (US)
Pages (from-to)1591-1602
Number of pages12
JournalCell
Volume159
Issue number7
DOIs
StatePublished - Dec 18 2014

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Tumors
Acetates
Acetyl Coenzyme A
Neoplasms
Carbon
Acetate-CoA Ligase
Gene Expression Regulation
Tumor Burden
Growth and Development
Histones
Energy Metabolism
Cell proliferation
Cell growth
Hepatocellular Carcinoma
Cell Survival
Metabolites
Metabolism
Gene expression
Nutrients
Cell Proliferation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Acetate dependence of tumors. / Comerford, Sarah A; Huang, Zhiguang; Du, Xinlin; Wang, Yun; Cai, Ling; Witkiewicz, Agnieszka; Walters, Holly; Tantawy, Mohammed N.; Fu, Allie; Manning, H. Charles; Horton, Jay D; Hammer, Robert E; McKnight, Steven L; Tu, Benjamin P.

In: Cell, Vol. 159, No. 7, 18.12.2014, p. 1591-1602.

Research output: Contribution to journalArticle

Comerford, SA, Huang, Z, Du, X, Wang, Y, Cai, L, Witkiewicz, A, Walters, H, Tantawy, MN, Fu, A, Manning, HC, Horton, JD, Hammer, RE, McKnight, SL & Tu, BP 2014, 'Acetate dependence of tumors', Cell, vol. 159, no. 7, pp. 1591-1602. https://doi.org/10.1016/j.cell.2014.11.020
Comerford SA, Huang Z, Du X, Wang Y, Cai L, Witkiewicz A et al. Acetate dependence of tumors. Cell. 2014 Dec 18;159(7):1591-1602. https://doi.org/10.1016/j.cell.2014.11.020
Comerford, Sarah A ; Huang, Zhiguang ; Du, Xinlin ; Wang, Yun ; Cai, Ling ; Witkiewicz, Agnieszka ; Walters, Holly ; Tantawy, Mohammed N. ; Fu, Allie ; Manning, H. Charles ; Horton, Jay D ; Hammer, Robert E ; McKnight, Steven L ; Tu, Benjamin P. / Acetate dependence of tumors. In: Cell. 2014 ; Vol. 159, No. 7. pp. 1591-1602.
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