ArticlePloS one2012
Nox4 mediates renal cell carcinoma cell invasion through hypoxia-induced interleukin 6- and 8- production.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Prognostic role of interleukin-6 in renal cell carcinoma: a meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Pooled it
- Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer.Frontiers in immunology · 2026Review
- IL-12 as a Potential Prognostic Marker in Penile Cancer: Implications for Immune Dysregulation.International journal of molecular sciences · 2025Article
- NOX4 Suppresses Ferroptosis Through Regulation of the Pentose Phosphate Pathway in Colorectal Cancer.Current medical science · 2025Article
- Inflammation in Penile Squamous Cell Carcinoma: A Comprehensive Review.International journal of molecular sciences · 2025Review
- NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion.Biological research · 2024Review
- An update to experimental and clinical aspects of tumor-associated macrophages in cancer development: hopes and pitfalls.Clinical and experimental medicine · 2024Review
- Multiple Applications of a Novel Fluorescence Probe with Large Stokes Shift and Sensitivity for Rapid HJournal of fluorescence · 2024Article
- Cellular and exosomal GPx1 are essential for controlling hydrogen peroxide balance and alleviating oxidative stress in hypoxic glioblastoma.Redox biology · 2023Article
- Inflammatory Networks in Renal Cell Carcinoma.Cancers · 2023Review
- Inflammation in Urological Malignancies: The Silent Killer.International journal of molecular sciences · 2023Review
- Intestinal microbiota regulates diabetes and cancer progression by IL-1β and NOX4 dependent signaling cascades.Cellular and molecular life sciences : CMLS · 2022Article
- IL6 and CCL18 Mediate Cross-talk between VHL-Deficient Kidney Cells and Macrophages during Development of Renal Cell Carcinoma.Cancer research · 2022Article
- NADPH Oxidase 4 (NOX4) in Cancer: Linking Redox Signals to Oncogenic Metabolic Adaptation.International journal of molecular sciences · 2022Review
- NADPH Oxidase 4: A Potential Therapeutic Target of Malignancy.Frontiers in cell and developmental biology · 2022Review
- Potential Key Markers for Predicting the Prognosis of Gastric Adenocarcinoma Based on the Expression of Ferroptosis-Related lncRNA.Journal of immunology research · 2022Article
- Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome.Frontiers in oncology · 2022Article
- Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms.International journal of molecular sciences · 2021Review
- PD-1 immunobiology in glomerulonephritis and renal cell carcinoma.BMC nephrology · 2021Review
- Nuclear NADPH oxidase-4 associated with disease progression in renal cell carcinoma.Translational research : the journal of laboratory and clinical medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInflammatory cytokines are detected in the plasma of patients with renal cell carcinoma (RCC) and are associated with poor prognosis. However, the primary cell type involved in producing inflammatory cytokines and the biological significance in RCC remain unknown. Inflammation is associated with oxidative stress, upregulation of hypoxia inducible factor 1-alpha, and production of pro-inflammatory gene products. Solid tumors are often heterogeneous in oxygen tension together suggesting that hypoxia may play a role in inflammatory processes in RCC. Epithelial cells have been implicated in cytokine release, although the stimuli to release and molecular mechanisms by which they are released remain unclear. AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status and a role for AMPK in the regulation of cell inflammatory processes has recently been demonstrated. METHODS AND PRINCIPAL
findingsWe have identified for the first time that interleukin-6 and interleukin-8 (IL-6 and IL-8) are secreted solely from RCC cells exposed to hypoxia. Furthermore, we demonstrate that the NADPH oxidase isoform, Nox4, play a key role in hypoxia-induced IL-6 and IL-8 production in RCC. Finally, we have characterized that enhanced levels of IL-6 and IL-8 result in RCC cell invasion and that activation of AMPK reduces Nox4 expression, IL-6 and IL-8 production, and RCC cell invasion. CONCLUSIONS/SIGNIFICANCE: Together, our data identify novel mechanisms by which AMPK and Nox4 may be linked to inflammation-induced RCC metastasis and that pharmacological activation of AMPK and/or antioxidants targeting Nox4 may represent a relevant therapeutic intervention to reduce IL-6- and IL-8-induced inflammation and cell invasion in RCC.
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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.