Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress

By Z. Schug, B. Peck, Dylan T. Jones, Qifeng Zhang, S. Grosskurth, Israt S. Alam, Louise M. Goodwin, Elizabeth Smethurst, S. Mason, K. Blyth and 23 more. Cancer Cell, 2015

766 citations recorded by the source corpus.

Summary 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/de31b9995c728f6b46b8092239d803b431d61ef8

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Citations in the corpus

Targeting Metabolism for Cancer Therapy (2017, background): “Some cancers are nevertheless dependent on expression of acetyl-CoA synthetase 2 (ACSS2), the cytosolic enzyme that allows cells to synthesize acetyl-CoA from acetate, making this represents a potential therapeutic target (Comerford et al., 2014; Schug et al., 2015).”
Metabolic reprogramming and epigenetic modifications on the path to cancer (2021, background): “Nuclear-localized ACSS2 maintains the levels of histone acetylation (Schug et al., 2015; Bulusu et al., 2017) (Fig.”
Lipid metabolism reprogramming and its potential targets in cancer (2018, background): “Indeed, cancer cells rely mainly on acetate as a carbon source for fatty acid synthesis under hypoxic conditions [74].”
Reprogramming of fatty acid metabolism in cancer (2019, background): “With regard to acetyl-CoA metabolism, tumours specifically upregulate ACSS2 under conditions of hypoxia or lipid deprivation, leading to increased acetate uptake and ligation with CoA to produce acetyl-CoA for de novo lipogenesis.(33) Importantly, a HIF–SREBF2 signalling axis drives ACSS2 expression”
Fundamentals of cancer metabolism (2016, background): “Although a major function of the mitochondria is to provide acetyl-CoA to the cell, cancer cells can also use acetate to support cell growth and survival during metabolic stress (hypoxia or nutrient deprivation) (96, 171).”
Acetyl coenzyme A: a central metabolite and second messenger. (2015, background): “Bloc1s1 / mouse embryonic fibroblasts indeed exhibit increased expression levels of TFEB and its downstream targets (Scott et al., 2014), providing yet another link between deacetylation and the activation of a pro-autophagic transcriptional program.”