ArticleOncogene2022
Macrophage-mediated RON signaling supports breast cancer growth and progression through modulation of IL-35.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 43 citations in OpenAlex.
- Loss of short-form Ron promotes B and T cell cooperation to prevent outgrowth of breast cancer bone metastasis.bioRxiv : the preprint server for biology · 2026Article
- Tumor-Derived Interleukin 35 Promotes Fibrosis in the Tumor Microenvironment of Pancreatic Cancer by Activating Pancreatic Stellate Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- IL35 modulates HBV-related HCC progression via IL6-STAT3 signaling.Scientific reports · 2025Article
- A generalized protocol for the induction of M2-like macrophages from mouse and rat bone marrow mononuclear cells.Biology methods & protocols · 2025Article
- Multi-omics analysis reveals the unique landscape of DLD in the breast cancer tumor microenvironment and its implications for immune-related prognosis.Computational and structural biotechnology journal · 2024Article
- Guardians and Mediators of Metastasis: Exploring T Lymphocytes, Myeloid-Derived Suppressor Cells, and Tumor-Associated Macrophages in the Breast Cancer Microenvironment.International journal of molecular sciences · 2024Review
- MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation.Journal of experimental & clinical cancer research : CR · 2024Article
- The Zeb1-Cxcl1 axis impairs the antitumor immune response by inducing M2 macrophage polarization in breast cancer.American journal of cancer research · 2024Article
- TRIM21-mediated Sohlh2 ubiquitination suppresses M2 macrophage polarization and progression of triple-negative breast cancer.Cell death & disease · 2023Article
- Targeting isoforms of RON kinase (MST1R) drives antitumor efficacy.Cell death and differentiation · 2023Article
- Review
- Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.Biomolecules · 2022Review
- RON (Cancers · 2022Article
- The role of IL-35 and IL-37 in breast cancer - potential therapeutic targets for precision medicine.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Tumor associated macrophages (TAMs) play a major role in regulating mammary tumor growth and in directing the responses of tumor infiltrating leukocytes in the microenvironment. However, macrophage-specific mechanisms regulating the interactions of macrophages with tumor cells and other leukocytes that support tumor progression have not been extensively studied. In this study, we show that the activation of the RON receptor tyrosine kinase signaling pathway specifically in macrophages supports breast cancer growth and metastasis. Using clinically relevant murine models of breast cancer, we demonstrate that loss of macrophage RON expression results in decreases in mammary tumor cell proliferation, survival, cancer stem cell self-renewal, and metastasis. Macrophage RON signaling modulates these phenotypes via direct effects on the tumor proper and indirectly by regulating leukocyte recruitment including macrophages, T-cells, and B-cells in the mammary tumor microenvironment. We further show that macrophage RON expression regulates the macrophage secretome including IL-35 and other immunosuppressive factors. Overall, our studies implicate activation of RON signaling in macrophages as a key player in supporting a thriving mammary pro-tumor microenvironment through novel mechanisms including the augmentation of tumor cell properties through IL-35.
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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.