Abstract PL02-01: The metabolic phase of the cell cycle.

Abstract

Abstract Due to the nature of tumorigenesis, cancer cells constantly encounter environments in which nutrient and oxygen availability is severely compromised. In order to survive these harsh conditions, cancer cell transformation is often coupled with large changes in metabolism necessary to satisfy the exigencies for energy and biomass imposed by continued cellular proliferation. These variations often involve increases in the consumption and metabolism of extracellular resources, such as glucose, amino acids, and lipids. We were particularly interested in investigating the role of lipid metabolism in cancer cell growth. A siRNA screen against a panel of genes involved in lipid metabolism, specifically identified acetyl-coA synthetase as a critical enzyme for the growth of breast and prostate cancer cells. Bioinformatics analyses revealed that acetyl-coA synthetase 2 (ACSS2) was indeed amplified in a subset of invasive breast carcinomas. Furthermore, we characterized the contribution of acetate to lipid metabolism through liquid chromatography/mass spectrometry-based metabolomics and lipidomic approaches. Induced silencing of ACSS2 reduced cell growth of both breast and prostate cancer cells and revealed a heretofore unappreciated role of acetate as an anabolic precursor for de novo lipid biogenesis and cell growth. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):PL02-01. Citation Format: Eyal Gottlieb. The metabolic phase of the cell cycle. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr PL02-01.