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Updated: Apr 19, 2026
11:32
Analytical Determination of Mitochondrial Function of Excised Solid Tumor Homogenates
Published on: August 6, 2021
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Acetate dependence of tumors
Sarah A Comerford1, Zhiguang Huang2, Xinlin Du2
1Department of Molecular Genetics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell
|December 20, 2014
Summary
The enzyme ACSS2 (acetyl-CoA synthetase 2) helps tumors grow by using acetate. Blocking ACSS2 significantly reduced tumor size in mice, suggesting it
Area of Science:
- Biochemistry
- Metabolic pathways
- Cancer biology
Background:
- Acetyl-CoA (AcCoA) is crucial for cellular energy, growth, and gene regulation.
- Tumors with high glycolysis or hypoxia rely on AcCoA for survival.
- ACSS2 is a key enzyme in AcCoA metabolism.
Purpose of the Study:
- To investigate the role of nucleocytosolic acetyl-CoA synthetase (ACSS2) in tumor metabolism.
- To determine if ACSS2 is a potential therapeutic target for cancer.
Main Methods:
- Mice lacking the ACSS2 enzyme were used.
- Tumor burden was assessed in two hepatocellular carcinoma models.
- Cellular acetate uptake and incorporation into lipids and histones were measured.
Main Results:
- Mice lacking ACSS2 showed a significant reduction in tumor burden.
- ACSS2 activity accounted for the majority of cellular acetate uptake.
- ACSS2 is expressed in a large proportion of human tumors.
Conclusions:
- ACSS2 is a critical source of AcCoA for tumors, utilizing acetate.
- ACSS2 represents a targetable metabolic vulnerability in a wide spectrum of tumors.
- Targeting ACSS2 may offer a novel therapeutic strategy for cancer treatment.
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