ArticleRedox biology2019
Tumoral NOX4 recruits M2 tumor-associated macrophages via ROS/PI3K signaling-dependent various cytokine production to promote NSCLC growth.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 123 papers, 1 of them a synthesis that pooled it.
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Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 200 citations in OpenAlex.
- A comprehensive analysis of the role of QPRT in breast cancer.Scientific reports · 2023Pooled it
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Research progress on the expression characteristics, biological functions, and therapeutic potential of NOX4 in malignant tumors: a functional perspective.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- NOX4 suppresses malignant progression in prostate adenocarcinoma and functions as a potential diagnostic biomarker.Translational andrology and urology · 2026Article
- The pyroptosis and inflammatory response-related long noncoding RNA signature as a novel prognostic biomarker of head and neck squamous cell carcinoma.Discover oncology · 2026Article
- SPINK4 affected M2 macrophage polarization to promote colorectal cancer malignant phenotype by PI3K/AKT pathway.BMC cancer · 2026Article
- Ginsenoside Rg1 Ameliorates LPS-Induced Sepsis-Associated Lung Injury in Mice via VEGFC/D-VEGFR3 Signaling-Mediated Lymphangiogenesis and Lymphatic Remodeling.The Kaohsiung journal of medical sciences · 2026Article
- PSMA-Targeting Macrophage Membrane-Coated Nanoparticles for Precision Diagnosis and Combination Therapy of Prostate Cancer.Exploration (Beijing, China) · 2026Article
- M2pep-modified liposomal nanoparticles delivering siITGB4 induce apoptosis and inhibit NSCLC metastasis via macrophage reprogramming.Apoptosis : an international journal on programmed cell death · 2026Article
- Molecular biology of targeting lymphangiogenesis in cancer: Therapeutic strategies and future promise.Fundamental research · 2026Review
- Macrophage-delivered Nifuroxazide reprograms immunosuppressive microenvironment and synergizes with oxaliplatin for enhanced anti-hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
- The distinct roles of ROS in tumor immunity: from mechanisms to immunotherapeutic applications.Journal of hematology & oncology · 2026Review
- Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.ImmunoTargets and therapy · 2026Review
- The Role of NADPH Oxidase 4 in Neutrophil-Mediated Immune Escape in Gastric Cancer.International journal of biological sciences · 2026Article
- The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets.Frontiers in immunology · 2026Review
- Immunosuppressive cell populations as potential drivers of extrinsic immune checkpoint inhibition resistance in clear cell renal cell carcinoma.Oncology reviews · 2026Review
- Redox Modulation in Hepatic Fibrosis: Translating NOX1/4 Inhibition to Therapy.International journal of molecular sciences · 2025Review
- Concurrent PIK3CA mutant promotes cachexia through inflammatory signaling in EGFR mutant lung cancer.Nature communications · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
M2-type tumor-associated macrophages (TAMs) infiltration contributes to cancer malignant progression. However, the mechanisms for controlling recruitment and M2 polarization of macrophages by cancer cells are largely unclear. NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and mediates cancer progression. NOXs are in close relation with cancer-related inflammation, nevertheless, whether tumoral NOXs influence microenvironmental macrophages remains undentified. This study found that there was a close association between NOX4 expression and macrophage chemotaxis in patients with NSCLC analyzed using TCGA RNA-sequencing data. NOX4 in NSCLC cells (A549 and Calu-1 cell lines) efficiently enhanced murine peritoneal macrophage migration and induces M2 polarization. Immunohistochemical analysis of clinical specimens confirmed the positive correlation of NOX4 and CD68 or CD206. The mechanical study revealed that tumoral NOX4-induced reactive oxygen species (ROS) stimulated various cytokine production, including CCL7, IL8, CSF-1 and VEGF-C, via PI3K/Akt signaling-dependent manner. Blockade of the function of these cytokines reversed NOX4 effect on macrophages. Specifically, the results showed that tumoral NOX4-educated M2 macrophages exhibited elevated JNK activity, expressed and released HB-EGF, thus facilitating NSCLC proliferation in vitro. Pretreatment of macrophages with JNK inhibitor blocked tumoral NOX4-induced HB-EGF production in M2 macrophages. Finally, in a xenograft mouse model, overexpression of NOX4 in A549 cells enhanced the tumor growth. Elimination of ROS by NAC or inhibition of NOX4 activity by GKT137831 suppressed tumor growth accompanied by reduction in macrophage infiltration and the percentage of M2 macrophages. In conclusion, our study indicates that tumoral NOX4 recruits M2 TAMs via ROS/PI3K signaling-dependent various cytokine production, thus contributing NSCLC cell growth.
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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.