ArticleCell death and differentiation2023
TRAF3/STAT6 axis regulates macrophage polarization and tumor progression.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
57 citing papers in PubMed, 66 citations in OpenAlex.
- Exploring the shared genetic architecture between post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA).European journal of psychotraumatology · 2026Article
- MicroRNA regulation of macrophage polarization in lung cancer: Regulatory networks and therapeutic potential (Review).International journal of oncology · 2026Review
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Therapeutic modulation of the vitreoretinal fibrosis microenvironment in female mice using engineered macrophage-derived extracellular vesicles.Nature communications · 2026Article
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- Transcription factors remodel tumor immune microenvironment by impacting multiple immune cells.Discover oncology · 2026Review
- Macrophages in lung cancer: principal factors, regulatory mechanisms, and therapeutic opportunities: a narrative review.Translational lung cancer research · 2026Review
- Real-Time In Vivo Visualization of Tumor-Associated Macrophage Reprogramming Using a Nitric Oxide-Activatable NIR-II Nanoinducer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inflammaging-induced TRAF3 degradation impairs AMP biosynthesis to drive sarcopenia.Research square · 2026Article
- STAT6: Multidimensional analysis from hematopoietic immune regulation to pathogenesis mechanisms and therapeutic targets in hematologic malignancies.Annals of hematology · 2026Review
- DNA-PK-mediated phosphorylation of STAT6 establishes a non-canonical type 2 immunity axis to prevent macrophage senescence.Nature communications · 2026Article
- 4-Octyl itaconate alleviates sepsis-induced liver injury by regulating ferroptosis via the OTUB1/TRAF3 axis.Scientific reports · 2026Article
- IL-18 promotes pancreatic fibrosis via release of IL-4 from pancreatic stellate cells and induces macrophage M2 polarization.Scientific reports · 2026Article
- Anti-Inflammatory and Protective Role of tiRNA-Glu-TTC-003 in Pediatric Sepsis Via TREM2/TLR4 Signaling Modulation.Inflammation · 2026Article
- The Role of Low CD36 Expression in the Development of Non-Small Cell Lung Cancer and Its Potential for Therapy.Cancers · 2026Review
- SOX4-STAT6-MTHFD2 axis drives hepatocellular carcinoma progression and treatment resistance.Cell death & disease · 2026Article
- SLC25A1-Mediated Cholesterol Accumulation Promotes Endometriosis Progression by Enhancing Endometrial Stromal Cell Proliferation, Invasion, and M2 Macrophage Polarization.International journal of biological sciences · 2026Article
- STAT6 inhibition of M2 macrophages suppresses tumor growth by modulating the tumor microenvironment in colon cancer model.Frontiers in immunology · 2026Article
- Clonal evolution and stromal crosstalk drive an invasive epithelial program in bladder cancer.Frontiers in cell and developmental biology · 2026Article
- The Role of Traditional Chinese Medicine in Metabolic Reprogramming, Tumor microenvironment, and Macrophage Regulation: Mechanisms and Advances in Preclinical Studies.Journal of Cancer · 2026Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Converting tumor-associated macrophages (TAMs) from the M2 to the M1 phenotype is considered an effective strategy for cancer therapy. TRAF3 is known to regulate NF-κB signaling. However, the role of TRAF3 in TAM polarization has not yet been completely elucidated. Here, we found that ablation of TRAF3 increased M1 markers, iNOS, FGR and SLC4A7, while down-regulated M2 markers, CD206, CD36 and ABCC3, expression levels in macrophages. Moreover, TRAF3 deficiency enhanced LPS-induced M1 and abolished IL-4-induced macrophage polarization. Next, quantitative ubiquitomics assays demonstrated that among the quantitative 7618 ubiquitination modification sites on 2598 proteins, ubiquitination modification of IL-4 responding proteins was the most prominently reduced according to enrichment analysis. STAT6, a key factor of IL-4 responding protein, K450 and K129 residue ubiquitination levels were dramatically decreased in TRAF3-deficient macrophages. Ubiquitination assay and luciferase assay demonstrated that TRAF3 promotes STAT6 ubiquitination and transcriptional activity. Site mutation analysis revealed STAT6 K450 site ubiquitination played a vital role in TRAF3-mediated STAT6 activation. Finally, B16 melanoma mouse model demonstrated that myeloid TRAF3 deficiency suppressed tumor growth and lung metastasis in vivo. Taken together, TRAF3 plays a vital role in M2 polarization via regulating STAT6 K450 ubiquitination in macrophages.
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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 Socratic graph.