ArticleJournal of experimental & clinical cancer research : CR2024
IL6-STAT3-C/EBPβ-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Research trends in lung cancer and the tumor microenvironment: a bibliometric analysis of studies published from 2014 to 2023.Frontiers in oncology · 2024Pooled it
- Beryllium Sulfate-Induced Cellular Senescence via the IL-6/STAT3 Pathway to Promote Pulmonary Fibrosis.Journal of applied toxicology : JAT · 2026Article
- Acetylation-dependent nuclear translocation of EXOC4 regulates KU70 methylation to facilitate non-homologous end joining.Cell death and differentiation · 2026Article
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- HIF-1-mediated PPME1 expression promotes breast cancer progression via AKT activation and β-catenin recruitment.The Journal of clinical investigation · 2026Article
- Epithelial-mesenchymal transition in carcinoma: navigating phenotypic states to target resistance and metastasis.Cancer metastasis reviews · 2026Review
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- NLRC5-Deficient Macrophages Promote a Tumor-Permissive Phenotype via AXL- and MERTK-Mediated Efferocytosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- Integrating network toxicology, machine learning, and single-cell sequencing systems to analyze autophagy core genes in lung adenocarcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Deciphering lung cancer at high resolution: a narrative review of applications of single-cell and spatial transcriptomics sequencing.Translational lung cancer research · 2026Review
- Integrin-mediated mechanotransduction in the tumor microenvironment: macrophage-centered signaling mechanisms and immune remodeling.Journal of translational medicine · 2026Review
- CXCL9/SPP1-polarized tumor-associated macrophages exert dual roles in regulating anti-tumor immunity in lung adenocarcinoma.Cancer immunology, immunotherapy : CII · 2026Article
- MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.Cell death & disease · 2026Article
- Microcystin-LR Impairs Endometrial Receptivity during the Peri-Implantation Window via Disruption of STAT3/HIF-1α Signaling.Environment & health (Washington, D.C.) · 2026Article
- Tedizolid Targets AQP9-JAK/STAT Axis to Suppress Metastatic Progression in Clear Cell Renal Cell Carcinoma: Mechanism and Therapeutic Implications.International journal of molecular sciences · 2026Article
- Exosomal 3'tiRNA-PheGAA and interleukin-6 as novel biomarkers for non-invasive detection of NSCLC.Discover oncology · 2026Article
- MOncogene · 2026Article
- ADAM9 in tumor biology: molecular functions, clinical implications, and therapeutic targeting.Cellular & molecular biology letters · 2026Review
- COLEC12high tumor-associated macrophages orchestrate lenvatinib resistance and cancer stemness in hepatocellular carcinoma via paracrine NRG1-HER2/HER3 signaling.Clinical and molecular hepatology · 2026Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer is one of the most common tumors in the world, and metastasis is one of the major causes of tumor-related death in lung cancer patients. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are frequently associated with tumor metastasis in human cancers. However, the regulatory mechanisms of TAMs in lung cancer metastasis remain unclear.
methodsSingle-cell sequencing analysis of lung cancer and normal tissues from public databases and from 14 patients who underwent surgery at Zhongshan Hospital was performed. In vitro co-culture experiments were performed to evaluate the effects of TAMs on lung cancer migration and invasion. Changes in the expression of IL-6, STAT3, C/EBPΒ, and EMT pathway were verified using RT-qPCR, western blotting, and immunofluorescence. Dual luciferase reporter assays and ChIP were used to reveal potential regulatory sites on the transcription factor sets. In addition, the effects of TAMs on lung cancer progression and metastasis were confirmed by in vivo models.
resultsTAM infiltration is associated with tumor progression and poor prognosis. IL-6 secreted by TAMs can activate the JAK2/STAT3 pathway through autocrine secretion, and STAT3 acts as a transcription factor to activate the expression of C/EBPβ, which further promotes the transcription and expression of IL-6, forming positive feedback loops for IL6-STAT3-C/EBPβ-IL6 in TAMs. IL-6 secreted by TAMs promotes lung cancer progression and metastasis in vivo and in vitro by activating the EMT pathway, which can be attenuated by the use of JAK2/STAT3 pathway inhibitors or IL-6 monoclonal antibodies.
conclusionsOur data suggest that TAMs promote IL-6 expression by forming an IL6-STAT3-C/EBPβ-IL6 positive feedback loop. Released IL-6 can induce the EMT pathway in lung cancer to enhance migration, invasion, and metastasis. The use of IL-6-neutralizing antibody can partially counteract the promotion of LUAD by TAMs. A novel mechanism of macrophage-promoted tumor progression was revealed, and the IL6-STAT3-C/EBPβ-IL6 signaling cascade may be a potential therapeutic target against lung cancer.
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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.