ArticleJCI insight2023
β-Catenin signaling in alveolar macrophages enhances lung metastasis through a TNF-dependent mechanism.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Inflammatory and neurotoxic risk of atorvastatin in diabetic peripheral neuropathy: TNF-centered evidence integrating network toxicology, scRNA-Seq, and cell validation.Frontiers in chemistry · 2026Article
- Semaphorin-7A promotes macrophage-mediated mammary epithelial and ductal carcinoma in situ invasion.Breast cancer research : BCR · 2025Article
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- Review
- PCDHGA10 as a Potential Biomarker of Lung Squamous Cell Carcinoma Based on Bioinformatics and Experimental Verification.Molecular biotechnology · 2025Article
- Emerging macrophage-based therapies for cancer: a review of preclinical and clinical advances.Frontiers in immunology · 2025Review
- Targeting the plasticity of intestinal neutrophils: bidirectional regulation strategies by natural products.Frontiers in immunology · 2025Review
- Immunotherapy strategies targeting tumor-associated macrophages and their mechanisms of action in tumor progression.Frontiers in immunology · 2025Review
- Alveolar macrophages maintain tissue localization and gain enhanced anti-tumor activity in Lewis lung carcinoma-reprogrammed lung microenvironment.Frontiers in immunology · 2025Article
- Tissue-Resident Macrophages in Cancer: Friend or Foe?Cancer medicine · 2024Review
- Apoptotic signaling pathways in bone metastatic lung cancer: a comprehensive analysis.Discover oncology · 2024Review
- Platelets favor the outgrowth of established metastases.Nature communications · 2024Article
- Downregulation of IRF8 in alveolar macrophages by G-CSF promotes metastatic tumor progression.iScience · 2024Article
- Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.Cell & bioscience · 2024Review
- The roles of tissue resident macrophages in health and cancer.Experimental hematology & oncology · 2024Review
- Understanding tissue-resident macrophages unlocks the potential for novel combinatorial strategies in breast cancer.Frontiers in immunology · 2024Review
- Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.Frontiers in immunology · 2024Review
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
The main cause of malignancy-related mortality is metastasis. Although metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment, especially macrophages, which correlate with poor clinical outcomes. Macrophages consist of bone marrow-derived and tissue-resident populations. In contrast to bone marrow-derived macrophages, the transcriptional pathways that govern the pro-metastatic activities of tissue-resident macrophages (TRMs) remain less clear. Alveolar macrophages (AMs) are a TRM population with critical roles in tissue homeostasis and metastasis. Wnt/β-catenin signaling is a hallmark of cancer and has been identified as a pathologic regulator of AMs in infection. We tested the hypothesis that β-catenin expression in AMs enhances metastasis in solid tumor models. Using a genetic β-catenin gain-of-function approach, we demonstrated that (a) enhanced β-catenin in AMs heightened lung metastasis; (b) β-catenin activity in AMs drove a dysregulated inflammatory program strongly associated with Tnf expression; and (c) localized TNF-α blockade abrogated this metastatic outcome. Last, β-catenin gene CTNNB1 and TNF expression levels were positively correlated in AMs of patients with lung cancer. Overall, our findings revealed a Wnt/β-catenin/TNF-α pro-metastatic axis in AMs with potential therapeutic implications against tumors refractory to the antineoplastic actions of TNF-α.
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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.