ArticleJournal of experimental & clinical cancer research : CR2025
Extracellular matrix stiffness regulates colorectal cancer progression via HSF4.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Development of a 3D-bioprinted tumour-on-chip with tunable hydrogel properties for monitoring colorectal cancer cell migration and invasion.Materials today. Bio · 2026Article
- CT-derived extracellular volume fraction and AI-assisted body composition for predicting neoadjuvant therapy response and prognosis in colorectal cancer.Abdominal radiology (New York) · 2026Article
- A Protocol for Colorectal Tumor Spheroid Culture in Tunable Stiffness Alginate-Based Hydrogels and Subsequent Immunohistochemical Analysis.Bio-protocol · 2026Article
- Mechanobiology of the tumor microenvironment: a review of therapeutic interactions and in vitro elasticity measurement techniques.Journal of biomedical science · 2026Review
- Advanced 3D cancer models for analyzing tumor-immune cell interaction and therapeutic response.Molecular cancer · 2026Review
- Leucovorin enhances curcumin-induced inhibition of cell viability and ferroptosis in colorectal cancer cells.Oncology letters · 2026Article
- Nanotechnology Meets Immunotherapy: Crosstalks Against Cancer.Immunity, inflammation and disease · 2026Review
- YAP1-driven tumor-like cancer-associated fibroblasts modulate biomechanics of pancreatic ductal adenocarcinoma.Journal of gastroenterology · 2026Article
- Dormancy in Metastatic Colorectal Cancer: Tissue Engineering Opportunities forTissue engineering. Part B, Reviews · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The 3D Collagen Network as a Determinant of Tumor Progression and Drug Delivery Efficiency in Breast Cancer.Pharmaceutics · 2026Review
- Integration of radiomics, deep learning, transcriptomics, and metabolomics reveals prognostic risk stratification and underlying biological mechanisms in colorectal cancer.NPJ precision oncology · 2026Article
- Deciphering Stiffness-Driven Changes in Colorectal Cancer by Proteomics.Molecular & cellular proteomics : MCP · 2026Article
- PLOD2 promotes proliferation, migration and invasion of colorectal cancer cells via PI3K-AKT-GSK3β signaling pathway.Scientific reports · 2026Article
- Article
- The tumor immune microenvironment of thyroid cancer and colorectal cancer: cellular crosstalk and therapeutic implications.Frontiers in immunology · 2026Review
- The role of thrombospondin-1 in dermatological conditions.Frontiers in medicine · 2026Review
- Nanodynamic Therapy in Colorectal Cancer: Engineering Precision Immunotherapy and Multimodal Synergy.International journal of nanomedicine · 2026Review
- Collagen-mediated pro-tumorigenic MAPK activation drives stromal-immune reprogramming in solid cancers.Frontiers in immunology · 2026Article
- Single-Cell Analysis Links C7+ Cancer-Associated Fibroblasts with Incomplete Resection in Platinum-Sensitive Relapsed Ovarian Cancer.Biomedicines · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) has high incidence and mortality rates, with severe prognoses during invasion and metastasis stages. Despite advancements in diagnostic and therapeutic technologies, the impact of the tumour microenvironment, particularly extracellular matrix (ECM) stiffness, on CRC progression and metastasis is not fully understood.
methodsThis study included 107 CRC patients. Tumour stiffness was assessed using magnetic resonance elastography (MRE), and collagen ratio was analysed with Masson staining. CRC cell lines were cultured on matrices of varying stiffness, followed by transcriptome sequencing to identify stiffness-related genes. An HSF4 knockout CRC cell model was cultured in different ECM stiffness to evaluate the effects of HSF4 on cell proliferation, migration, and invasion in vitro and in vivo.
resultsCRC tumour stiffness was significantly higher than normal tissue and positively correlated with collagen content and TNM staging. High-stiffness matrices significantly regulated cell functions and signalling pathways. High HSF4 (heat shock transcriptional factor 4) expression was strongly associated with tumour stiffness and poor prognosis. HSF4 expression increased with higher TNM stages, and its knockout significantly inhibited cell proliferation, migration, and invasion, especially on high-stiffness matrices. In vivo experiments confirmed that HSF4 promoted tumour growth and metastasis, independent of collagen protein increase.
conclusionsThis study reveals that tumour stiffness promotes the proliferation and metastasis of CRC by regulating EMT-related signalling pathways through HSF4. Tumour stiffness and HSF4 could be valuable targets for prognostic assessment and therapeutic intervention in CRC.
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