ArticleBritish journal of cancer2023
AMPK phosphorylates and stabilises copper transporter 1 to synergise metformin and copper chelator for breast cancer therapy.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R-Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cation homeostasis-related prognostic genes uncovered by transcriptomic analysis in breast cancer.Translational cancer research · 2026Article
- Copper transporters promote the malignant progression of glioblastoma by regulating the immunosuppressive tumour microenvironment via the SLC31A1-WNT5A axis.Journal of translational medicine · 2026Article
- CDK4 Mediates Cisplatin Resistance in Renal Cell Carcinoma (RCC) Cells by Regulating the ASH1L-CTR1 Axis.Oncology research · 2026Article
- Targeting SH3GL1 for prognosis and immune response in breast cancer.Journal of pharmaceutical analysis · 2026Article
- Unraveling Diabetes Mellitus-Driven Tumorigenesis: From Pathophysiological Mechanisms, Therapeutic Drugs to Tailor-Made Nanosystems.International journal of nanomedicine · 2026Review
- Disruption of NF-κB-Mediated Copper Homeostasis Sensitizes Breast Cancer to Cuproptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Elesclomol-Induced Copper Influx Attenuates Lung Adenocarcinoma Progression With Involvement of the ER Stress/PCK2 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Regulation of Trace Metal Elements in Cancer Ferroptosis.Advanced biology · 2025Review
- Nanoparticles induced cuproptosis to enhance antitumor immunotherapy.Journal of nanobiotechnology · 2025Review
- CRISPR screening approaches in breast cancer research.Cancer metastasis reviews · 2025Review
- A novel taxane SB-T-101141 triggers a noncanonical ferroptosis to overcome Paclitaxel resistance of breast cancer via iron homeostasis-related KHSRP.Cell death & disease · 2025Article
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- AKT1 Phosphorylates FDX1 to Promote Cuproptosis Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Unveiling the Origin of Copper Accumulation in Plasma with Aging.Environment & health (Washington, D.C.) · 2025Article
- Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.Frontiers in pharmacology · 2025Review
- Strategies to combat cancer drug resistance: focus on copper metabolism and cuproptosis.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Roles of Copper Transport Systems Members in Breast Cancer.Cancer medicine · 2024Review
- Cuproptosis: unveiling a new frontier in cancer biology and therapeutics.Cell communication and signaling : CCS · 2024Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPredominant roles of copper and its transporter, copper transporter 1 (CTR1), in tumorigenesis have been explored recently; however, the upstream regulation of CTR1 and combinational intervention of copper chelators in malignancies remain largely unclear.
methodsCRISPR/Cas9-based kinome screening was used to identify the CTR1 upstream kinases. Immunofluorescence assays were utilised to detect CTR1 localisation. In vitro kinase assays and mass spectrometry were performed to detect CTR1 phosphorylation. Ubiquitination assays were performed to validate CTR1 stability. Colony formation, EdU labelling, Annexin V-FITC/PI-based apoptosis assays were carried out to detect the drug effect on cell growth and apoptosis. Xenografted mouse models were employed to investigate drug effects in vivo.
resultsWe identify that CTR1 undergoes AMPK-mediated phosphorylation, which enhances CTR1 stabilisation and membrane translocation by affecting Nedd4l interaction, resulting in increased oncogenic roles in breast cancer. Importantly, activation of AMPK with its agonist metformin markedly enhances CTR1 levels, and leads to the combinational usage of AMPK agonists and copper chelators for breast cancer treatment.
conclusionsOur findings not only reveal the crosstalk between energy response and copper uptake via AMPK-mediated CTR1 phosphorylation and stability but also highlight the strategy to combat breast cancer by a combination of AMPK agonists and copper chelators. SIGNIFICANCE: The connection between energy response and copper homoeostasis is linked by AMPK phosphorylating and stabilising CTR1, which provides a promising strategy to combat breast cancer by combining AMPK agonists and copper chelators.
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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.