ArticleScientific reports2017
TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Advancements and trends in exosome research in lung cancer from a bibliometric analysis (2004-2023).Frontiers in oncology · 2024Pooled it
- TRAF6 as a potential target in advanced breast cancer: a systematic review, meta-analysis, and bioinformatics validation.Scientific reports · 2023Pooled it
- The CaInternational journal of molecular sciences · 2026Article
- [Comprehensive Analysis of the Expression, Prognosis and Function of TRAF Family Proteins in NSCLC].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Article
- Involvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.Genes & diseases · 2025Review
- Article
- Fibroblasts as Turned Agents in Cancer Progression.Cancers · 2023Review
- Nanoparticles overcome adaptive immune resistance and enhance immunotherapyFrontiers in pharmacology · 2023Review
- Role of K63-linked ubiquitination in cancer.Cell death discovery · 2022Review
- TRAF4 Inhibits Bladder Cancer Progression by Promoting BMP/SMAD Signaling.Molecular cancer research : MCR · 2022Article
- LncRNA HCG18 upregulates TRAF4/TRAF5 to facilitate proliferation, migration and EMT of epithelial ovarian cancer by targeting miR-29a/b.Molecular medicine (Cambridge, Mass.) · 2022Article
- The Research Progress in Physiological and Pathological Functions of TRAF4.Frontiers in oncology · 2022Review
- TRAF4 Inhibits the Apoptosis and Promotes the Proliferation of Breast Cancer Cells by Inhibiting the Ubiquitination of Spindle Assembly-Associated Protein Eg5.Frontiers in oncology · 2022Article
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Micronutrient imbalance and common phenotypes in neural tube defects.Genesis (New York, N.Y. : 2000) · 2021Review
- Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms.Molecular cancer · 2021Review
- Tumor microenvironment: a prospective target of natural alkaloids for cancer treatment.Cancer cell international · 2021Review
- Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.Nature communications · 2021Article
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
- The Ubiquitin Proteasome System and Skin Fibrosis.Molecular diagnosis & therapy · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Normal fibroblasts surrounding tumor cells play a crucial role in cancer progression through formation of the tumor microenvironment. Because factors secreted from normal fibroblasts can modulate the tumor microenvironment, it is necessary to identify key factors associated with regulation of secreted factors and to investigate the molecular mechanisms contributing to the tumor microenvironment formation process. In this study, we found that radiation induced the expression and K63-linkage poly-ubiquitination of TRAF4 in normal lung fibroblasts. The K63-linkage poly-ubiquitinated TRAF4 formed complexes with NOX2 or NOX4 by mediating phosphorylated p47-phox in normal lung fibroblasts. Moreover, we showed that TRAF4 stabilized NOX complexes by decreasing lysosomal degradation of NOX2 and NOX4 after irradiation. NOX complexes increased endosomal ROS levels that were permeable into cytoplasm, leading to NF-κB-mediated ICAM1 up-regulation. Soluble ICAM1 was subsequently secreted into conditioned media of radiation-activated normal lung fibroblasts. The conditioned media from irradiated normal fibroblasts enhanced proliferation and epithelial-mesenchymal transition of non-small cell lung cancer cells both in vitro and in vivo. These results demonstrate that TRAF4 in irradiated fibroblasts is positively associated with aggressiveness of adjacent cancer cells by altering the tumor microenvironment. Thus, we suggest that regulation of TRAF4 might be a promising strategy for cancer therapy.
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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.