ArticleNature communications2021
Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 288 citations in OpenAlex.
- The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.Frontiers in oncology · 2022Pooled it
- Suppression of LncRNA AC008406.3 sensitizes breast cancer cells to docetaxel via triggering cuproptosis.Cancer biology & therapy · 2026Article
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Unveiling the Impact of Copper Metabolism on Epithelial-Mesenchymal Transition of Triple-Negative Breast Cancer: Identification of Therapeutic Targets.Interdisciplinary sciences, computational life sciences · 2026Article
- Review
- Copper depletion boosts CNS leukemia therapy by inhibiting nucleotide synthesis through impairment of mitochondrial complex IV activity.Nature cancer · 2026Article
- The Role of Metal Ions in Mitochondria: From Energy Metabolism to Cell Destiny.Biological trace element research · 2026Review
- Engineering cuproptosis with nanomedicine: Design, combination therapy, and translation in cancer.Materials today. Bio · 2026Review
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- From copper imbalance to immunometabolic remodeling: cuproptosis-related vulnerability and therapeutic hypotheses in autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Tumor CTR1 Expression and Systemic Copper Dynamics Converge on a Copper Axis in High-Grade Triple-Negative Breast Cancer.Cancer research communications · 2026Article
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Copper Depletion Nanoparticles Potentiate Cancer Immunotherapy by Avoiding Innate and Adaptive Immune Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lipogenesis-driven EGFR palmitoylation enables metastatic immune evasion in triple-negative breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Research Progress of Cuproptosis in Orthopaedics: Opportunities and Challenges.Journal of cellular and molecular medicine · 2026Review
- Copper deprivation reprograms antioxidant defense to suppress ferroptosis via SLC7A11.Redox biology · 2026Article
- A novel LncRNA signature associated with cuproptosis for prognostic prediction and immune response assessment in rectum adenocarcinoma.Discover oncology · 2026Article
- CuET promotes cuproptosis and ferroptosis of lung cancer cells by interacting directly with polyunsaturated phospholipids.iScience · 2026Article
- Copper Transporter 1‑Mediated Deregulation of Copper Homeostasis Impacts MYC and Oxidative Phosphorylation Pathways and Increases the Sensitivity of Tumor Cells to Complex I Inhibitors.ACS pharmacology & translational science · 2026Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and a marked sensitivity to TM. Global proteomic and metabolomic profiling identifies TM-mediated inactivation of Complex IV as the primary metabolic defect in the SOX2/OCT4+ cell population. We also identify AMPK/mTORC1 energy sensor as an important downstream pathway and show that AMPK inhibition rescues TM-mediated loss of invasion. Furthermore, loss of the mitochondria-specific copper chaperone, COX17, restricts copper deficiency to mitochondria and phenocopies TM-mediated alterations. These findings identify a copper-metabolism-metastasis axis with potential to enrich patient populations in next-generation therapeutic trials.
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Registered trials
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.