ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
Copper Promotes Tumorigenesis by Activating the PDK1-AKT Oncogenic Pathway in a Copper Transporter 1 Dependent Manner.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 1 of them a synthesis that pooled it.
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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
121 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Cuproptosis as a therapeutic target in cancer: a Systematic Review and bibliometric analysis of the research landscape.Frontiers in oncology · 2025Pooled it
- RNF research trends and an RNF43-based prognostic model for colorectal cancer with immune microenvironment analysis.Discover oncology · 2026Article
- Copper-based metal-organic frameworks: applications and prospects in cancer diagnosis and therapy.RSC advances · 2026Review
- Targeting Copper in Cancer: Chelators to Counteract Cuproplasia and Ionophores to Promote Cuproptosis.Journal of medicinal chemistry · 2026Review
- Copper homeostasis and cuproptosis rewire the tumor microenvironment: mechanisms, immune modulation, and therapeutic opportunities.Journal of hematology & oncology · 2026Review
- MKRN1 suppresses cuproptosis in colorectal cancer through ubiquitin-dependent regulation of SLC31A1.Biological procedures online · 2026Article
- Blockage of cuproplasia inhibits pancreatic tumour-associated neutrophils infiltration through TRAF6/STAT3/CCL2 pathway.British journal of cancer · 2026Article
- Copper homeostasis and cuproptosis in cancer: mitochondrial metabolic dependency and nanomedicine-based therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Copper transporters promote the malignant progression of glioblastoma by regulating the immunosuppressive tumour microenvironment via the SLC31A1-WNT5A axis.Journal of translational medicine · 2026Article
- Copper deprivation reprograms antioxidant defense to suppress ferroptosis via SLC7A11.Redox biology · 2026Article
- An Activity-Based Sensing Approach to Monitor Nanomaterial-Promoted Changes in Labile Metal Pools in Living Systems.Chemical & biomedical imaging · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- SLC31A1 exon 1 methylation reduces intracellular copper ion and promotes diabetic cardiac fibrosis.Cardiovascular diabetology · 2026Article
- ZNF384-regulated SLC31A1 expression promotes tumor proliferation and invasion in breast cancer.Molecular and cellular biochemistry · 2026Article
- Role of cuproptosis in digestive system tumors (Review).International journal of molecular medicine · 2026Review
- Metallic elements and their molecular roles in gastric cancer: Pathogenic mechanisms and therapeutic implications.World journal of gastrointestinal oncology · 2026Review
- Copper homeostasis and cuproptosis in tumor biology: mechanistic insights and clinical perspectives.Frontiers in immunology · 2026Review
- Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer.International journal of biological sciences · 2026Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Copper plays pivotal roles in metabolic homoeostasis, but its potential role in human tumorigenesis is not well defined. Here, it is revealed that copper activates the phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB, also termed AKT) oncogenic signaling pathway to facilitate tumorigenesis. Mechanistically, copper binds 3-phosphoinositide dependent protein kinase 1 (PDK1), in turn promotes PDK1 binding and subsequently activates its downstream substrate AKT to facilitate tumorigenesis. Blocking the copper transporter 1 (CTR1)-copper axis by either depleting CTR1 or through the use of copper chelators diminishes the AKT signaling and reduces tumorigenesis. In support of an oncogenic role for CTR1, the authors find that CTR1 is abnormally elevated in breast cancer, and is subjected by NEDD4 like E3 ubiquitin protein ligase (Nedd4l)-mediated negative regulation through ubiquitination and subsequent degradation. Accordingly, Nedd4l displays a tumor suppressive function by suppressing the CTR1-AKT signaling. Thus, the findings identify a novel regulatory crosstalk between the Nedd4l-CTR1-copper axis and the PDK1-AKT oncogenic signaling, and highlight the therapeutic relevance of targeting the CTR1-copper node for the treatment of hyperactive AKT-driven cancers.
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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 Socratic graph.