ArticleMetallomics : integrated biometal science2020
Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation.
Article in Metallomics : integrated biometal science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses 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
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.
- Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).International journal of oncology · 2024Pooled it
- Pooled it
- A prognostic cuproptosis-related lncRNA predictive signature for bladder cancer patients.Human cell · 2023Trial
- Harnessing copper-iron crosstalk: A novel strategy to combat hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2026Review
- Engineering cuproptosis with nanomedicine: Design, combination therapy, and translation in cancer.Materials today. Bio · 2026Review
- Copper homeostasis and cuproptosis: molecular mechanisms and therapeutic opportunities.Molecular biomedicine · 2026Review
- Prognostic value and therapeutic potential of the cuproptosis-related gene LOXL2 in thyroid cancer.Translational oncology · 2026Article
- Hyperattenuation on non-enhanced CT and T2 hypointensity: an imaging pattern frequently associated with fibrous or smooth muscle-rich abdominal and pelvic lesions.Abdominal radiology (New York) · 2026Review
- Xuefu Zhuyu Decoction Reduces Excessive Collagen Deposition and Crosslinking in Myocardial Fibrosis via CTR1-Copper-LOX Axis.Chinese journal of integrative medicine · 2026Article
- 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 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
- 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
- A study on the role of cuproptosis-related immune checkpoint genes in non-small cell lung cancer.Medicine · 2026Article
- Multi-Omics Evidence Based on Spatial Transcriptomics Data Reveals the Therapeutic Value of Copper Death Genes in Glioblastoma.International journal of genomics · 2026Article
- Multiscale computational genomics in Wilson disease: from atomic dynamics to clinical prediction.Frontiers in genetics · 2026Review
- Association of Copper with Atherosclerosis and Treatment Strategies.Journal of cardiovascular translational research · 2025Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Targeting cuproptosis in liver cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC), the most common primary liver cancer, of which ∼800 000 new cases will be diagnosed worldwide this year, portends a five-year survival rate of merely 17% in patients with unresectable disease. This dismal prognosis is due, at least in part, from the late stage of diagnosis and the limited efficacy of systemic therapies. As a result, there is an urgent need to identify risk factors that contribute to HCC initiation and provide targetable vulnerabilities to improve patient survival. While myriad risk factors are known, elevated copper (Cu) levels in HCC patients and the incidence of hepatobiliary malignancies in Wilson disease patients, which exhibit hereditary liver Cu overload, suggests the possibility that metal accumulation promotes malignant transformation. Here we found that expression of the Cu transporter genes ATP7A, ATP7B, SLC31A1, and SLC31A2 was significantly altered in liver cancer samples and were associated with elevated Cu levels in liver cancer tissue and cells. Further analysis of genomic copy number data revealed that alterations in Cu transporter gene loci correlate with poorer survival in HCC patients. Genetic loss of the Cu importer SLC31A1 (CTR1) or pharmacologic suppression of Cu decreased the viability, clonogenic survival, and anchorage-independent growth of human HCC cell lines. Mechanistically, CTR1 knockdown or Cu chelation decreased glycolytic gene expression and downstream metabolite utilization and as a result forestalled tumor cell survival after exposure to hypoxia, which mimics oxygen deprivation elicited by transarterial embolization, a standard-of-care therapy used for patients with unresectable HCC. Taken together, these findings established an association between altered Cu homeostasis and HCC and suggest that limiting Cu bioavailability may provide a new treatment strategy for HCC by restricting the metabolic reprogramming necessary for cancer cell survival.
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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.