ArticleThe Journal of clinical investigation2021
Myeloid cell-derived PROS1 inhibits tumor metastasis by regulating inflammatory and immune responses via IL-10.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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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
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- The prognostic value of absolute lymphocyte count and neutrophil-to-lymphocyte ratio for patients with metastatic breast cancer: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- TYRO3, AXL, MERTK and Their Ligands in Brain Metastases From Colorectal Cancers.Cancer medicine · 2026Article
- Exploring and experimental validation of SLC7A11 and ferroptosis related prognostic genes in non-small cell lung cancer using bulk RNA sequencing and single-cell RNA sequencing.Biology direct · 2026Article
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- Association of IL4I1Frontiers in immunology · 2026Article
- Electroacupuncture attenuates synovitis in knee osteoarthritis and is associated with modulation of the protein S-TAM (Axl/MerTK)-Rac1 signaling axis.Frontiers in immunology · 2026Article
- Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.Journal of advanced research · 2025Article
- Role of the TLR signaling pathway in the pathogenesis of glioblastoma multiforme with an emphasis on immunotherapy.Biochemistry and biophysics reports · 2025Review
- Development and validation of a prognostic prediction model based on coagulation-related genes and clinical factors in acute leukemia.Translational pediatrics · 2025Article
- PCV2 Infection Upregulates SOCS3 Expression to Facilitate Viral Replication in PK-15 Cells.Viruses · 2025Article
- PROS1-MERTK Axis Drives Tumor Microenvironment Crosstalk and Progression in Papillary Thyroid Microcarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.Communications biology · 2025Article
- Integrated Metabolomics and Spatial Transcriptomics of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism as a Biomarker of Progression.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Circulating chemokines and leukocytes and their impact on breast cancer prognosis.Discover oncology · 2025Article
- Gpr109A in TAMs promoted hepatocellular carcinoma via increasing PKA/PPARγ/MerTK/IL-10/TGFβ induced M2c polarization.Scientific reports · 2025Article
- Mechanistic insights into PROS1 inhibition of bladder cancer progression and angiogenesis via the AKT/GSK3β/β-catenin pathway.Scientific reports · 2025Article
- Spatial profiling of the metabolism-immune axis in ovarian cancer.Frontiers in pharmacology · 2025Review
- Integrative Spatial Transcriptomics and Experimental Validation Reveal UBC-Mediated EMT Associated with Immune Evasion in Hepatocellular Carcinoma.ImmunoTargets and therapy · 2025Article
- Syndrome Differentiation and Treatment of Psoriasis by Traditional Chinese Medicines: An Integrating Study of Multi-Omics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulation of TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases promotes tumor progression through numerous cellular mechanisms. TAM cognate ligands GAS6 and PROS1 (for TYRO3 and MERTK) are secreted by host immune cells, an interaction which may support tumor progression. Here, we revealed an unexpected antimetastatic role for myeloid-derived PROS1: suppressing metastatic potential in lung and breast tumor models. Pros1 deletion in myeloid cells led to increased lung metastasis, independent of primary tumor infiltration. PROS1-cKO bone marrow-derived macrophages (BMDMs) led to elevated TNF-α, IL-6, Nos2, and IL-10 via modulation of the Socs3/NF-κB pathway. Conditioned medium from cKO BMDMs enhanced EMT, ERK, AKT, and STAT3 activation within tumor cells and promoted IL-10-dependent invasion and survival. Macrophages isolated from metastatic lungs modulated T cell proliferation and function, as well as expression of costimulatory molecules on DCs in a PROS1-dependent manner. Inhibition of MERTK kinase activity blocked PROS1-mediated suppression of TNF-α and IL-6 but not IL-10. Overall, using lung and breast cancer models, we identified the PROS1/MERTK axis within BMDMs as a potent regulator of adaptive immune responses with a potential to suppress metastatic seeding and revealed IL-10 regulation by PROS1 to deviate from that of TNF-α and IL-6.
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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.