2. Academic Validation
  3. Acetate dependence of tumors

Acetate dependence of tumors

  • Cell. 2014 Dec 18;159(7):1591-602. doi: 10.1016/j.cell.2014.11.020.
Sarah A Comerford 1,  Zhiguang Huang 2,  Xinlin Du 2,  Yun Wang 2,  Ling Cai 2,  Agnes K Witkiewicz 3,  Holly Walters 1,  Mohammed N Tantawy 4,  Allie Fu 5,  H Charles Manning 6,  Jay D Horton 1,  Robert E Hammer 2,  Steven L McKnight 7,  Benjamin P Tu 8
Affiliations

Affiliations

  • 1 Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • 2 Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • 3 Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • 4 Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 5 Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 6 Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 7 Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].
  • 8 Department of Biochemistry, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: [email protected].
PMID: 25525877 DOI: 10.1016/j.cell.2014.11.020
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.

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