ArticleExperimental & molecular medicine2025
Cancer-associated fibroblast-derived fibulin-5 promotes epithelial-mesenchymal transition in diffuse-type gastric cancer via cAMP response element-binding protein pathway, showing poor prognosis.
Article in Experimental & molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- Cadmium Exposure Facilitates Oral Squamous Cell Carcinoma Progression and Epithelial-mesenchymal Transition Through the Upregulation of ATP1B4.Biological trace element research · 2026Article
- Fibulin-5 (FBLN5) as a context-dependent pan-cancer regulator: integrated multi-omics analysis reveals dual roles in tumor progression and therapeutic resistance.Translational cancer research · 2026Article
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- A combined computational and functional approach identifies FBLN5 as an amino acid metabolism-related gene and suppressing colorectal cancer progression.Molecular genetics and genomics : MGG · 2026Article
- Unveiling prognostic genes and regulatory mechanisms of stress granules in gastric cancers: an integrated analysis of bulk transcriptomics and single-cell RNA sequencing.Frontiers in oncology · 2026Article
- Yin Yang 1 activates JAK-STAT3-mediated epithelial-mesenchymal transition inWorld journal of clinical oncology · 2025Article
- Exosome-derived Menin from cancer-associated fibroblasts promotes gastric cancer progression by activating the HSPA6/JNK/JunD pathway and inducing EMT.Journal of translational medicine · 2025Article
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Authors and funding
17 authors.
Funding
Abstract
Diffuse-type gastric cancer (DGC), characterized by poorly cohesive cells within fibrotic stroma, is associated with advanced disease and poor prognosis. Here, to identify distinct biomarkers for DGC compared with intestinal-type gastric cancer, we constructed a comprehensive large-scale signaling network using RNA-sequencing data from three genomic databases (The Cancer Genome Atlas, GSE62254 and GSE26253), developed a mathematical model and conducted simulation analyses. For validation, we used tissue microarray blocks of gastric cancers with immunohistochemical staining, single-cell RNA sequencing, primary cultures of cancer-associated fibroblasts (CAFs) and organoids, and a co-culture system involving CAFs and cancer cells. Signaling network analysis identified six differentially activated signaling components across the database, including BIRC5, TTK, NEK2, FHL1, NR2F1 and FBLN5. Among the differentially activated signaling components, high tumoral expression of fibulin-5 protein encoded by FBLN5 correlated with poor overall and disease-specific survival rates in patients with DGC, even after adjusting for the tumor, node, metastases (TNM) stage. Fibulin-5, derived from CAFs within DGC stroma, promoted organoid growth and epithelial-mesenchymal transition (EMT) in DGC cell lines via the cAMP response element-binding protein (CREB) pathway in a CAF co-culture system. FBLN5 knockdown in CAFs reduced the aggressive phenotype of co-cultured DGC cells, while CREB inhibitors reversed EMT. Furthermore, levels of secreted FBLN5 in patient blood samples correlated with its expression in primary tumors. In summary, fibulin-5 secreted by CAFs and interacted with DGC cells promotes EMT and is clinically associated with poor patient outcomes. These findings suggest fibulin-5 as a potential prognostic marker and therapeutic target in patients with DGC.
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