ArticleInternational journal of biological sciences2025
Integrative Single-Cell and Spatial Transcriptomics Analysis Reveals ECM-remodeling Cancer-associated Fibroblast-Derived POSTN as a Key Mediator in Pancreatic Ductal Adenocarcinoma Progression.
Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- TFPI2 in tumor metastasis: a double-edged sword with clinical implications.Cancer biology & therapy · 2026Review
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- Deep Learning-Assisted Prioritization of Candidate Drug Targets in Tumors Using Spatial Multi-Omics.Biology · 2026Review
- Cancer-associated fibroblast-derived POSTN as a metabolic "switch" shapes lipid-stressed macrophage polarization in gastric cancer.Redox biology · 2026Article
- APOEScience advances · 2026Article
- Scleral Postn Drives Myopia via Promoting Myofibroblast Transdifferentiation.Investigative ophthalmology & visual science · 2026Article
- Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial-Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes.International journal of molecular sciences · 2026Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Serum amyloid A1 promote progression of breast cancer and is associated with epithelial-mesenchymal transition.Translational cancer research · 2026Article
- A single-cell multi-omics atlas defines the cellular and molecular landscape of gastric intestinal metaplasia.Journal of translational medicine · 2026Article
- Integrative multimodal transcriptomics identifies a cancer-associated fibroblast membrane signature for predicting prognosis and therapeutic response in pancreatic ductal adenocarcinoma.Journal of molecular medicine (Berlin, Germany) · 2026Article
- POSTNOncology reports · 2026Article
- Spatially-resolved subtype progression reveals metabolic vulnerabilities in pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- Integrative multi-omics and radiogenomic profiling decodes NNK-related tumor remodeling and prognostic stratification in pancreatic cancer.International journal of surgery (London, England) · 2026Article
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- A postoperative recurrence prediction model for intrahepatic cholangiocarcinoma based on multi-omics analysis of adjacent-to-tumor tissues.Frontiers in oncology · 2026Article
- KRAS-driven cytokine-metabolic crosstalk shapes immune exclusion in pancreatic ductal adenocarcinoma.Frontiers in genetics · 2026Review
- Periostin: A matricellular protein with a multifaceted role in tumorigenesis (Review).International journal of molecular medicine · 2025Review
- Fragile X mental retardation 1 gene FMR1 promotes proliferation, migration, and invasion of gastric cancer cells via c-MYC.Journal of translational medicine · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) presents significant clinical challenges owing to its dense stroma and complex tumor microenvironment (TME). In this study, large-scale single-cell transcriptomics and spatial transcriptomics (ST) were integrated to dissect the heterogeneity of fibroblasts and their crosstalk with epithelial cells, with a focus on key ligand-receptor interactions. Eight distinct fibroblast subpopulations were identified, among which extracellular matrix (ECM)-remodeling fibroblasts were particularly enriched in tumor tissues and associated with poor prognosis. ECM-remodeling fibroblasts were located at the terminal stage of the fibroblast pseudotime trajectory, and SOX11 was identified as a key transcription factor in this subpopulation. Further analyses revealed that ECM-remodeling fibroblasts can interact with epithelial cells through the POSTN-ITGAV/ITGB5 ligand-receptor axis, a critical pathway that promotes tumor progression. Clinical analyses demonstrated a strong correlation between POSTN expression and poor prognosis in patients with PDAC. Mechanistically, POSTN interacts with integrin ITGAV/ITGB5 on tumor cells, activating the PI3K/AKT/β-catenin pathway and promoting epithelial-mesenchymal transition (EMT) phenotype. Pharmacological inhibition of the POSTN-integrin axis partially reversed these malignant traits, highlighting its potential as a therapeutic target. This study provides new insights into fibroblast heterogeneity and its role in PDAC progression, emphasizing the POSTN-ITGAV/ITGB5 axis as a promising target for therapeutic interventions.
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