ArticleThe Biochemical journal2019
Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity.
Article in The Biochemical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Engineered bacteria reverses tumor cuproptosis resistance via cancer-associated fibroblast reprogramming for enhanced immunotherapy.Materials today. Bio · 2026Article
- Research progress on TMEM proteins in cancer progression and chemoresistance (Review).International journal of molecular medicine · 2025Review
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases.Frontiers in immunology · 2025Review
- Mechanism of action and therapeutic value of anoctamin-1 in gastrointestinal cancers.Frontiers in immunology · 2025Review
- Cuproptosis-Related Genes MTF1 and LIPT1 as Novel Prognostic Biomarker in Acute Myeloid Leukemia.Biochemical genetics · 2024Article
- The Association between NADPH Oxidase 2 (NOX2) and Drug Resistance in Cancer.Current cancer drug targets · 2024Review
- An association between ATP7B expression and human cancer prognosis and immunotherapy: a pan-cancer perspective.BMC medical genomics · 2023Article
- Ion Channels as Potential Tools for the Diagnosis, Prognosis, and Treatment of HPV-Associated Cancers.Cells · 2023Review
- A zinc metabolism-related gene signature for predicting prognosis and characteristics of breast cancer.Frontiers in immunology · 2023Article
- Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas.Cancers · 2022Article
- TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
- Pan-cancer genetic analysis of cuproptosis and copper metabolism-related gene set.Frontiers in oncology · 2022Article
- A cuproptosis and copper metabolism-related gene prognostic index for head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- Relationships of Cuproptosis-Related Genes With Clinical Outcomes and the Tumour Immune Microenvironment in Hepatocellular Carcinoma.Pathology oncology research : POR · 2022Article
- Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma.Frontiers in immunology · 2022Article
- Cuproptosis-related LncRNAs are potential prognostic and immune response markers for patients with HNSCC via the integration of bioinformatics analysis and experimental validation.Frontiers in oncology · 2022Article
- Recurrent Human Papillomavirus-Related Head and Neck Cancer Undergoes Metabolic Reprogramming and Is Driven by Oxidative Phosphorylation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors' platinum resistance identifies novel approach to treating these tumors.
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