Ets-1 regulates energy metabolism in cancer cells

• Published in: PloS one Vol. 5; no. 10; p. e13565
• Main Authors: Verschoor, Meghan L, Wilson, Leigh A, Verschoor, Chris P, Singh, Gurmit
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.10.2010; Public Library of Science (PLoS)
• Subjects: Angiogenesis; Antioxidants; Bioinformatics; Biosynthesis; Cancer; Cancer cells; Cancer therapies; Cell Biology/Gene Expression; Cell culture; Citric acid; Data analysis; DNA microarrays; Electron transport; Electron transport chain; Energy metabolism; Energy Metabolism - physiology; Enzymes; ETS protein; Ets-1 protein; Extracellular matrix; Fatty acids; Female; Gene Expression; Genes; Genetics and Genomics/Cancer Genetics; Genetics and Genomics/Gene Expression; Glucose metabolism; Glycolysis; Humans; Lung cancer; Melanoma; Metabolism; Mitochondria; Mitochondrial DNA; Molecular Biology; Oligonucleotide Array Sequence Analysis; Oncology/Breast Cancer; Oncology/Gynecological Cancers; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Overexpression; Oxidative metabolism; Oxidative phosphorylation; Oxidative stress; Oxygen; Oxygen Consumption; Phosphorylation; Physiological aspects; Prostate cancer; Protein arrays; Protein expression; Proteins; Proto-Oncogene Protein c-ets-1 - physiology; Reactive oxygen species; Reverse Transcriptase Polymerase Chain Reaction; Thyroid cancer; Transcription factors; Tricarboxylic acid cycle; Ontario Canada; Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0013565

Cancer cells predominantly utilize glycolysis for ATP production even in the presence of abundant oxygen, an environment that would normally result in energy production through oxidative phosphorylation. Although the molecular mechanism for this metabolic switch to aerobic glycolysis has not been fully elucidated, it is likely that mitochondrial damage to the electron transport chain and the resulting increased production of reactive oxygen species are significant driving forces. In this study, we have investigated the role of the transcription factor Ets-1 in the regulation of mitochondrial function and metabolism. Ets-1 was over-expressed using a stably-incorporated tetracycline-inducible expression vector in the ovarian cancer cell line 2008, which does not express detectable basal levels of Ets-1 protein. Microarray analysis of the effects of Ets-1 over-expression in these ovarian cancer cells shows that Ets-1 up-regulates key enzymes involved in glycolysis and associated feeder pathways, fatty acid metabolism, and antioxidant defense. In contrast, Ets-1 down-regulates genes involved in the citric acid cycle, electron transport chain, and mitochondrial proteins. At the functional level, we have found that Ets-1 expression is directly correlated with cellular oxygen consumption whereby increased expression causes decreased oxygen consumption. Ets-1 over-expression also caused increased sensitivity to glycolytic inhibitors, as well as growth inhibition in a glucose-depleted culture environment. Collectively our findings demonstrate that Ets-1 is involved in the regulation of cellular metabolism and response to oxidative stress in ovarian cancer cells.