ArticlePloS one2011
Cellular model of Warburg effect identifies tumor promoting function of UCP2 in breast cancer and its suppression by genipin.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 144 citations in OpenAlex.
- Deformability screening identifies NUDT5 as a mediator of cellular mechanobiology.bioRxiv : the preprint server for biology · 2026Article
- Insights into the molecular and genetic role of obesity in breast cancer pathogenesis.Cancer biology & therapy · 2025Review
- Mitochondrial uncoupling, energy substrate utilization, and brown adipose tissue as therapeutic targets in cancer.npj metabolic health and disease · 2025Review
- Epicatechin DecreasesInternational journal of molecular sciences · 2025Article
- Genipin-Simple but Significant Bioactive Iridoid for Therapeutical Application and Beyond: A Review.Life (Basel, Switzerland) · 2025Review
- The Role of Mitochondrial Solute Carriers SLC25 in Cancer Metabolic Reprogramming: Current Insights and Future Perspectives.International journal of molecular sciences · 2024Review
- Density Gradient Centrifugation Is an Effective Tool to Isolate Cancer Stem-like Cells from Hypoxic and Normoxia Triple-Negative Breast Cancer Models.International journal of molecular sciences · 2024Article
- Genipin's potential as an anti-cancer agent: from phytochemical origins to clinical prospects.Medical oncology (Northwood, London, England) · 2024Review
- The Epstein-Barr virus-miRNA-BART6-5p regulates TGF-β/SMAD4 pathway to induce glycolysis and enhance proliferation and metastasis of gastric cancer cells.Oncology research · 2024Article
- Selenoproteins and the senescence-associated epitranscriptome.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- UCP2 as a Cancer Target through Energy Metabolism and Oxidative Stress Control.International journal of molecular sciences · 2022Review
- Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature.International journal of molecular sciences · 2022Review
- PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation.Antioxidants (Basel, Switzerland) · 2022Article
- Mechanism of tonifying-kidney Chinese herbal medicine in the treatment of chronic heart failure.Frontiers in cardiovascular medicine · 2022Review
- Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics.Frontiers in cell and developmental biology · 2022Article
- Dual imaging of dendritic spines and mitochondriaNeurobiology of stress · 2021Article
- UCP-2 inhibitor enhanced the efficacy of trastuzumab against HER2 positive breast cancer cells.Cancer chemotherapy and pharmacology · 2021Article
- Genipin enhances the antitumor effect of elesclomol in A549 lung cancer cells by blocking uncoupling protein-2 and stimulating reactive oxygen species production.Oncology letters · 2020Article
- On the Origin of ATP Synthesis in Cancer.iScience · 2020Review
- The influence of photodynamic therapy on the Warburg effect in esophageal cancer cells.Lasers in medical science · 2020Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
The Warburg Effect is characterized by an irreversible injury to mitochondrial oxidative phosphorylation (OXPHOS) and an increased rate of aerobic glycolysis. In this study, we utilized a breast epithelial cell line lacking mitochondrial DNA (rho(0)) that exhibits the Warburg Effect associated with breast cancer. We developed a MitoExpress array for rapid analysis of all known nuclear genes encoding the mitochondrial proteome. The gene-expression pattern was compared among a normal breast epithelial cell line, its rho(0) derivative, breast cancer cell lines and primary breast tumors. Among several genes, our study revealed that over-expression of mitochondrial uncoupling protein UCP2 in rho(0) breast epithelial cells reflects gene expression changes in breast cancer cell lines and in primary breast tumors. Furthermore, over-expression of UCP2 was also found in leukemia, ovarian, bladder, esophagus, testicular, colorectal, kidney, pancreatic, lung and prostate tumors. Ectopic expression of UCP2 in MCF7 breast cancer cells led to a decreased mitochondrial membrane potential and increased tumorigenic properties as measured by cell migration, in vitro invasion and anchorage independent growth. Consistent with in vitro studies, we demonstrate that UCP2 over-expression leads to development of tumors in vivo in an orthotopic model of breast cancer. Genipin, a plant derived small molecule, suppressed the UCP2 led tumorigenic properties, which were mediated by decreased reactive oxygen species and down-regulation of UCP2. However, UCP1, 3, 4 and 5 gene expression was unaffected. UCP2 transcription was controlled by SMAD4. Together, these studies suggest a tumor-promoting function of UCP2 in breast cancer. In summary, our studies demonstrate that i) the Warburg Effect is mediated by UCP2; ii) UCP2 is over-expressed in breast and many other cancers; iii) UCP2 promotes tumorigenic properties in vitro and in vivo and iv) genipin suppresses the tumor promoting function of UCP2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.