ArticleMedComm2025
PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis.
Article in MedComm, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- CXCL11 recruits immunosuppressive cells to form a barrier at the invasive front of pancreatic cancer by activating the NF-κB/CCL2 axis.Translational oncology · 2026Article
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Article
- BGN/MDK Axis in the Melanoma Tumor Microenvironment Strengthens Tumor Malignancy by Modulating Cancer Cells and Cancer-Associated Fibroblasts Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances in protein microarray-based proteomics for gastric cancer applications in biomarker discovery, molecular subtyping, and precision oncology.Frontiers in oncology · 2026Review
- Targeting Cancer-Associated Fibroblasts in Prostate Cancer: Recent Advances and Therapeutic Opportunities.Cancers · 2025Review
- Cancer-associated fibroblasts in the tumor microenvironment: heterogeneity, crosstalk mechanisms, and therapeutic implications.Molecular cancer · 2025Review
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- CC/CXC chemokine risk signature at single-cell resolution: a machine learning model for precision stratification in cervical cancer.Translational cancer research · 2025Article
- Non-coding RNAs in gastric cancer: mechanisms and therapeutic prospects.Molecular cancer · 2025Review
- Exosomal CCT6A Secreted by Cancer-Associated Fibroblasts Interacts with β-Catenin to Enhance Chemoresistance and Tumorigenesis in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
- Unraveling the breast cancer tumor microenvironment: crucial factors influencing natural killer cell function and therapeutic strategies.International journal of biological sciences · 2025Review
- ARID3A Promotes Tumor Progression by Activating TNF-α/NF-κB Signaling in Dual-Phenotype Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2025Article
- PDPN+ cancer-associated fibroblasts enhance gastric cancer angiogenesis via AKT/NF-κB activation and the CCL2-ACKR1 axis.MedComm · 2025Article
- Inflammatory factors collaboratively linkFrontiers in immunology · 2025Review
- Research on Buyang Yiwei Decoction in the Treatment of Gastric Cancer Based on PI3K/AKT Signaling Pathway: A Review.Cancer management and research · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) are intrinsic components of the tumor microenvironment that promote cancer progression and metastasis. Through an unbiased integrated analysis of gastric tumor grade and stage, we identified a subset of proangiogenic CAFs characterized by high podoplanin (PDPN) expression, which are significantly enriched in metastatic lesions and secrete chemokine (CC-motif) ligand 2 (CCL2). Mechanistically, PDPN(+) CAFs enhance angiogenesis by activating the AKT/NF-κB signaling pathway. The canonical NF-κB signaling protein P65 binds to the promoter region of CCL2, inducing its expression. Additionally, we found that CCL2 interacts with its nonclassical receptor ACKR1 (expressed on endothelial cells) to exert its proangiogenic effects. Furthermore, the disruption of CCL2-ACKR1 communication via a CCL2 neutralizing antibody or the inhibition of AKT signaling transduction using AKT inhibitors effectively suppressed tumor growth. Together, this study elucidates the mechanism by which PDPN(+) CAFs promote angiogenesis, providing a deeper understanding of the molecular processes underlying CAF-mediated angiogenesis and suggesting potential therapeutic targets for gastric cancer treatment.
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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.