ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2022
Cancer-associated fibroblasts-derived HAPLN1 promotes tumour invasion through extracellular matrix remodeling in gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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85 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Cancer-associated fibroblasts, and clinicopathological characteristics and prognosis of gastric cancer: A systematic review and meta-analysis.Frontiers in oncology · 2023Pooled it
- Enhanced Transdermal Delivery of rhHAPLN1 by SoluballPharmaceutics · 2026Article
- Review
- MFAP2 secreted by TGF-β1-induced cancer-associated fibroblast cells promotes gastric cancer peritoneal metastasis through Src-STAT3-PTK7 axis.Cell death discovery · 2026Article
- PDLSC-CM targets HAPLN1 in macrophages to reduce root resorption in delayed replanted teeth.Stem cell research & therapy · 2026Article
- A seven-gene diagnostic and prognostic signature for papillary thyroid carcinoma.Discover oncology · 2026Article
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Histology-defined activated cancer-associated fibroblasts are associated with poor survival in diffuse-type gastric adenocarcinoma.Virchows Archiv : an international journal of pathology · 2026Article
- Tumor Budding in Gastric Carcinoma: Beyond Counting Cells at the Invasive Front-A Review of Current Evidence and Biological Perspectives.International journal of molecular sciences · 2026Review
- Targeting CAFs-derived PCSK6 inhibits redistribution of PD-L1 and restores response of CD8Cell death and differentiation · 2026Article
- A Novel Telomere Maintenance Gene-Related Model for Prognosis Prediction in Gastric Cancer.Biochemical genetics · 2026Article
- Combining Spatial Transcriptomics and Machine Learning Unravels Fibroblast-Related Biomarkers in Ulcerative Colitis.Inflammation · 2026Article
- Integrating single-cell and bulk transcriptomes with machine learning reveals a CAF signature for immunotherapy response in dMMR endometrial cancer.Discover oncology · 2026Article
- From Tumor Biology to Clinical Perspectives: Novel Biomarkers and Therapeutic Insights in Gastric Cancer.Oncology research · 2026Review
- Diagnostic and prognostic values of differentially expressed genes in canine mammary carcinoma: An integrated bioinformatics analysis.PloS one · 2026Article
- Perspective on the integration of radiomics and spatial omics in the analysis of the tumor microenvironment of bladder cancer and prospects for precision diagnosis and treatment.Frontiers in immunology · 2026Review
- Article
- CT-derived extracellular volume fraction as a predictive marker for postoperative recurrence in pStage II-III gastric cancer.European radiology · 2026Article
- Cancer-Associated Fibroblasts in Gastrointestinal Cancer Metastasis: Mechanisms and Emerging Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Therapy-educated fibroblast states link treatment pressure to residual disease and acquired resistance in gastric cancer.Frontiers in immunology · 2026Review
25 more citing papers are in PubMed but not listed here.
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9 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer-associated fibroblasts (CAFs) are the most principal cells of depositing and remodeling extracellular matrix (ECM) within solid tumours. Both CAFs and ECM have been demonstrated to play critical roles in tumour development. However, the functional roles of CAFs-associated ECM or ECM remodeling in the pathogenesis of gastric cancer remain unclear.
methodsBioinformatics analysis of the differentially expressed genes between CAFs and corresponding normal fibroblasts (NFs) in gastric cancer was performed. The clinical relevance of hyaluronan and proteoglycan link protein 1 (HAPLN1) was investigated using TCGA data and human gastric cancer specimens. Spheroid cell invasion assay and nude mouse xenograft model were introduced to assay cell invasion. Second harmonic generation (SHG) was used to image and analyze the changes of collagen fibers in ECM.
resultsHAPLN1 was identified as the most significantly up-regulated gene in CAFs of gastric cancer, and higher HAPLN1 levels were associated with shorter overall survival. HAPLN1 was prominently produced by CAFs, and its levels were correlated positively with tumor T staging (P < 0.0001), lymph node metastasis (P = 0.0006) and TNM stage (P = 0.0063). Mechanically, gastric cancer cells activate fibroblasts to up-regulate HAPLN1 expression via activation of TGF-β1/Smad2/3 signaling, which in turn promotes tumour migration and invasion. Importantly, SHG assays with mouse xenograft models and human samples further demonstrated CAFs-derived HAPLN1 increased tumour invasiveness through ECM remodeling.
conclusionsThis study sheds light on the role of CAFs-derived HAPLN1 in the pathogenesis of gastric cancer, and provides insights for the development of novel strategies for prevention and treatment of gastric carcinoma.
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