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Cited by 59Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

Ets-1 regulates energy metabolism in cancer cells

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Verschoor, Meghan L., Wilson, Leigh A., Verschoor, Chris P., Singh, Gurmit·2010·PLoS ONE
DOI 10.1371/journal.pone.0013565PMC PMC2962648
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Abstract

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.

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Cited by

Sorted by citations

Authors
Verschoor, M. L., Wilson, L. A., Verschoor, C. P., & Singh, G.
Affiliations
  • Juravinski Cancer Centre (CA)
  • McMaster University (CA)
Corresponding author
Singh, Gurmit
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2010-10-22
Volume
5
Issue
10
Pages
e13565
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0013565
PMC
PMC2962648
OpenAlex
W1968468939
Cited by
59
References
1
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 8 · 2012: 4
FWCI
1.23
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Canadian Institutes of Health Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
ETS1, transcription factors, cancer cell energy metabolism, aerobic glycolysis, Warburg effect, mitochondrial function, electron transport chain, reactive oxygen species, oxidative stress, antioxidant defense, fatty acid metabolism, TCA cycle, oxygen consumption, glycolysis inhibitors, glucose deprivation, ovarian cancer, gene expression regulation
MeSH terms
Energy Metabolism, Female, Glycolysis, Humans, Ovarian Neoplasms, Oxygen Consumption, Gene Expression, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Proto-Oncogene Protein c-ets-1

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