ArticleScientific reports2015
Tetrathiomolybdate inhibits mitochondrial complex IV and mediates degradation of hypoxia-inducible factor-1α in cancer cells.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Review
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- Targeting cuproptosis for treatment and prognostic assessment in endometrial cancer.Cancer cell international · 2025Review
- Decoding cuproptosis and cuproplasia: implications for therapeutic strategies in renal cell carcinoma.Cell death discovery · 2025Review
- Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells.Science advances · 2025Article
- Identification of copper metabolism-related subtypes, the development of a prognosis model, and characterization of the immune landscape in colorectal cancer.Discover oncology · 2025Article
- The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer.Signal transduction and targeted therapy · 2025Review
- Cuproplasia and cuproptosis, two sides of the coin.Cancer communications (London, England) · 2025Review
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Immune microenvironment and molecular mechanisms in endometrial cancer: implications for resistance and innovative treatments.Discover oncology · 2025Review
- The emerging role of cuproptosis in spinal cord injury.Frontiers in immunology · 2025Review
- A new peptide inhibitor of C1QBP exhibits potent anti-tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair.Clinical and translational medicine · 2025Article
- Copper and Colorectal Cancer.Cancers · 2024Review
- Selenium, Zinc, and Plasma Total Antioxidant Status and the Risk of Colorectal Adenoma and Cancer.Metabolites · 2024Article
- Targeting mitochondrial quality control: new therapeutic strategies for major diseases.Military Medical Research · 2024Review
- Hypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies.Redox biology · 2024Review
- Forchlorfenuron-Induced Mitochondrial Respiration Inhibition and Metabolic Shifts in Endometrial Cancer.Cancers · 2024Article
- Copper in Gynecological Diseases.International journal of molecular sciences · 2023Review
- The huge potential of targeting copper status in the treatment of colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that triggers adaptive responses upon low oxygen conditions and plays a crucial role in cancer metabolism and therapy resistance. Tetrathiomolybdate (TM), a therapy option for copper overload disorder, has also been shown to be capable of limiting tumor angiogenesis, although its underlying mechanism remains unclear. Using ovarian and endometrial cancer cell lines, we observed that TM downregulates HIF-1α protein levels and HIF-transcriptional targets involved in tumor angiogenesis and glycolysis, but did not affect HIF-1α protein synthesis. TM-mediated HIF-1α downregulation was suppressed when HIF-prolyl hydroxylase activity was pharmacologically inhibited using deferoxamine or dimethyloxaloylglycine, and also when the oxygen-dependent degradation domains of HIF-1α, which are responsible for the interaction with HIF-prolyl hydroxylase, were deleted. These findings suggest that TM causes HIF-1α downregulation in a HIF-prolyl hydroxylase-dependent manner. Our studies showed that TM inhibits the activity of the copper-dependent mitochondrial complex IV and reduces mitochondrial respiration, thereby possibly increasing oxygen availability, which is crucial for HIF-prolyl hydroxylase activity. Pimonidazole staining also showed that TM elevates oxygen tension in hypoxic cells. Our studies provide mechanistic evidence for TM-mediated HIF-1α regulation and suggest its therapeutic potential as a method of blocking angiogenesis in ovarian and endometrial tumors.
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