ArticleOncotarget2017
Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Plasminogen Activation System and Fibroblasts: Impact on Tissue Remodeling, Disease, and Organ Homeostasis.Inflammation · 2026Review
- Multiomics immune profiling of a patient-relevant orthotopic lung cancer model using SEPARATE-Seq.Nature communications · 2026Article
- Soluble urokinase plasminogen activator receptor is a prognostic biomarker in decompensated cirrhosis.JHEP reports : innovation in hepatology · 2026Article
- Piezo1: the Potential Novel Target for Radiation-induced Liver Fibrosis by Regulating FAP + fibroblasts.Molecular and cellular biochemistry · 2025Review
- Profibrinolytic Factors and Cancer Progression, Metastasis, and Survival.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Urokinase Plasminogen Activation System Modulation in Transformed Cell Lines.International journal of molecular sciences · 2025Article
- [Colorectal fibroblasts promote malignant phenotype of colorectal cancer cells by activating the ERK signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Dysregulated fibrinolysis and plasmin activation promote the pathogenesis of osteoarthritis.JCI insight · 2024Article
- New Immunohistochemical Markers for Pleural Mesothelioma Subtyping.Diagnostics (Basel, Switzerland) · 2023Article
- Role of cancer-associated fibroblasts in the progression, therapeutic resistance and targeted therapy of oesophageal squamous cell carcinoma.Frontiers in oncology · 2023Review
- Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers.Cancer cell international · 2022Review
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Role of Serine Proteases at the Tumor-Stroma Interface.Frontiers in immunology · 2022Review
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- FAP-Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts.Advanced functional materials · 2021Article
- Salivary KLK5 and uPA are potential biomarkers for malignant transformation of OLK and OLP.Cancer biomarkers : section A of Disease markers · 2021Article
- CCL3-CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche.Cancer management and research · 2020Review
- Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?Frontiers in immunology · 2020Review
- Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) are believed to influence tumor behavior and clinical outcomes. We previously showed that conditioned medium (CM) from CAFs induces proliferation and motility of esophageal squamous cell carcinoma (ESCC) cells. Here, we investigated the molecular mechanisms by which the CAF-secreted proteins induce ESCC development and progression. Using antibody arrays, we identified urokinase plasminogen activator (uPA) as one of the main proteins whose release was increased in CAFs compared to normal fibroblasts (NFs). Immunohistochemical analysis of pathological sections showed that uPA-positive cells were localized at the boundaries of tumor and stroma tissues, in stroma between tumor nests, and within the tumors. Increased stromal uPA levels (132/146 cases) correlated with tumor invasion (p < 0.05) and overall survival of ESCC patients (p < 0.05). In vitro assays showed that uPA promotes ESCC cell proliferation, migration, and invasion via PI3K/AKT and ERK signaling pathways. In vivo, anti-uPA antibody suppressed tumor growth in ESCC xenografts. These results suggest that uPA released from stroma, and especially from CAFs, might be a predictive marker for ESCC diagnosis and prognosis, as well as an effective therapeutic target.
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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.