ArticleOncogene2019
NF-κB-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 71 citations in OpenAlex.
- Research trends and cellular targets of NF-κB pathway in acute lung injury [2005-2024]: a combined bibliometric analysis and systematic review.Journal of thoracic disease · 2026Article
- Rethinking Oxidative Stress inLife (Basel, Switzerland) · 2026Review
- CXCL16 Promotes the Development of Chronic Atrophic Gastritis by Regulating M1 Macrophage Polarisation.Journal of inflammation research · 2026Article
- Classification based on tumor phenotypes enables the novel molecular characterization of esophagogastric junction cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Multimodal Artificial Intelligence-Based Virtual Biopsy for Diagnosing Abdominal Lavage Cytology-Positive Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Study the Impact of NADPH oxidase1,TNF-alpha and Cyclooxygenase-2 On Colon Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Ferroptosis in idiopathic pulmonary fibrosis: mechanisms, impact, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Ferroptosis: opening up potential targets for gastric cancer treatment.Molecular and cellular biochemistry · 2024Review
- NoxO1 Determines the Level of ROS Formation by the Nox1-Centered NADPH Oxidase.Antioxidants (Basel, Switzerland) · 2024Article
- Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma.Bioactive materials · 2024Article
- Review
- Porphyromonas gingivalis Lipopolysaccharide Damages Mucosal Barrier to Promote Gastritis-Associated Carcinogenesis.Digestive diseases and sciences · 2024Article
- Interaction between intestinal flora and gastric cancer in tumor microenvironment.Frontiers in oncology · 2024Review
- Review
- Frequent loss of metastatic ability in subclones of Apc, Kras, Tgfbr2, and Trp53 mutant intestinal tumor organoids.Cancer science · 2023Article
- The role and mechanism of NADPH oxidase in the development and progression of thyroid carcinoma.American journal of cancer research · 2023Review
- The Novel Protein ADAMTS16 Promotes Gastric Carcinogenesis by Targeting IFI27 through the NF-κb Signaling Pathway.International journal of molecular sciences · 2022Article
- Host Cell Antimicrobial Responses againstInternational journal of molecular sciences · 2022Review
- Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy.Pharmaceutics · 2022Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously showed that NADPH oxidase organizer 1 (Noxo1), a component of NADPH oxidase 1 (NOX1), is a TNF-α-induced tumor-promoting factor in gastric tumorigenesis. However, the mechanism of NOX1-induced reactive oxygen species (ROS) signaling for the gastric tumorigenesis has not been understood. Here, we showed that expression of NOX1 complex components, including Noxo1, but not other NOX family members was significantly upregulated in both mouse models for gastritis and gastric tumors, which was associated with increased ROS levels. We also found that NF-κB directly regulated NOXO1 expression in TNF-α-stimulated gastric cancer cells, suggesting that inflammation induces NOX1 complex activation through TNF-α/NF-κB pathway. Notably, in situ hybridization indicated that Noxo1 mRNA was detected in proliferating cells of gastritis and gastric tumors, and pharmacological inhibition of NOX activity significantly suppressed the proliferation of MKN45 gastric cancer cells and gastric hyperplasia of K19-C2mE mice. These results suggest that NOX1/ROS signaling has an important role in increased proliferation of stomach epithelial cells in the inflamed mucosa. Moreover, we found that expression of SOX2, a marker of gastric epithelial stem cells, was increased by NOX1/ROS signaling. Furthermore, disruption of Noxo1 in K19-C2mE mice significantly suppressed gastritis-associated metaplastic hyperplasia, a potent preneoplastic lesion, which was associated with decreased number of SOX2-positive cells. These results indicate that inflammation-induced Noxo1 expression is responsible for development of metaplastic hyperplasia in the stomach through an increase in SOX2-expressing undifferentiated epithelial cells. Therefore, inhibition of the NOX1/ROS signaling pathway is a possible strategy for prevention and therapy for gastric cancer development.
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