ArticleCell death discovery2021
PLAU directs conversion of fibroblasts to inflammatory cancer-associated fibroblasts, promoting esophageal squamous cell carcinoma progression via uPAR/Akt/NF-κB/IL8 pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- The PLAU-ITGB1-TGF-β axis orchestrates spatiotemporal reprogramming of fibroblasts at the invasive front to drive dual immunosuppressive niche and immunotherapy resistance in oral squamous cell carcinoma.Cell death & disease · 2026Article
- Pre-existing antibodies predict protection while mucosal inflammation correlates with symptomaticmedRxiv : the preprint server for health sciences · 2026Article
- Identifying PLAU as a shared pathogenic gene in type 2 diabetes and bladder urothelial carcinoma through integrated transcriptomic analysis and machine learning for diagnostic and therapeutic value.Clinical and experimental medicine · 2026Article
- Identification of an Anoikis-Related Gene Signature to Predict the Prognosis in Patients With Oral Squamous Cell Carcinoma.International dental journal · 2026Article
- OSBPL3 promotes LUAD metastasis and glycolysis through transcriptional upregulation of PLAU via NFE2L2.Translational oncology · 2026Article
- Exosomal FOSL1 From Cancer-associated Fibroblasts Drives the Progression and Pro-tumorigenic M2 Macrophage Polarization of Hepatocellular Carcinoma By Activating PLAU Transcription.Applied biochemistry and biotechnology · 2026Article
- Article
- Integrated Transcriptomics and Experimental Validation Reveal That Ellagic Acid Alleviates Fuchs Endothelial Corneal Dystrophy via PLAU/NF-κB Signaling.Investigative ophthalmology & visual science · 2026Article
- Baicalein inhibits the progression of thyroid cancer by suppressing the TPL2/MEK2/ERK2 pathway.Frontiers in endocrinology · 2026Article
- LAMP5 as a novel prognostic biomarker linked to the tumor immune microenvironment in esophageal squamous cell carcinoma.American journal of cancer research · 2026Article
- Downregulated PLAU alleviates acute rejection after liver transplantation by targeting Ptgs2 in macrophages.Frontiers in immunology · 2026Article
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- Cancer-associated fibroblasts are associated with neo-adjuvant treatment response in oesophageal adenocarcinoma.British journal of cancer · 2025Article
- Stromal PLAU mediates tumor progression and informs a novel therapeutic target in triple-negative breast cancer.Cancer cell international · 2025Article
- Article
- Chronic Wound Initiation: Single-Cell RNAseq of Cutaneous Wound Tissue and Contributions of Oxidative Stress to Initiation of Chronicity.Antioxidants (Basel, Switzerland) · 2025Article
- Integrated multi-omics analysis reveals key hub genes and mechanisms in calcific aortic stenosis.Frontiers in cardiovascular medicine · 2025Article
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Crotonylation-Related Prognostic Model of Esophageal Squamous Cell Carcinoma Based on Transcriptome Analysis and Single-Cell Sequencing Analysis.International journal of general medicine · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) plays an important role in the tumor microenvironment. The heterogeneity of CAFs affects the effect of CAFs on promoting or inhibiting tumors, which can be regulated by other cells in the tumor microenvironment through paracrine methods. The urokinase-type plasminogen activator (PLAU) system mediates cell proliferation, migration, adhesion, and other functions through the proteolytic system, intracellular signal transduction, and chemokine activation. PLAU promotes tumor progression in many tumors. We explored the function of PLAU in ESCC and the influence of PLAU secreted by tumor cells on the heterogeneity of CAFs. We found that PLAU is highly expressed in ESCC, which is related to poor prognosis and can be used as a prognostic marker for ESCC. Through loss-of function and gain-of function experiments, we found that PLAU promoted ESCC proliferation and clone formation via MAPK pathway, and promotes migration by upregulating Slug and MMP9, which can be reversed by the MEK 1/2 inhibitor U0126. At the same time, through sequencing, cytokine detection, and RT-qPCR verification, we found that tumor cells secreted PLAU promoted the conversion of fibroblasts to inflammatory CAFs, which upregulated expression and secretion of IL8 via the uPAR/Akt/NF-κB pathway. The IL8 secreted by CAFs in turn promotes the high expression of PLAU in tumor cells and further promoted the progression of ESCC. In summary, PLAU was not only a prognostic marker of ESCC, which promoted tumor cell proliferation and migration, but also promoted the formation of inflammatory CAFs by the PLAU secreted by tumor cells.
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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.