ArticlePloS one2015
Higher Matrix Stiffness Upregulates Osteopontin Expression in Hepatocellular Carcinoma Cells Mediated by Integrin β1/GSK3β/β-Catenin Signaling Pathway.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells.Immunity · 2026Article
- Identifying vascular stiffening-sensitive macrophages through integration of single-cell transcriptomics and imaging flow cytometry.Biophysics reports · 2025Article
- Osteopontin attenuates the foreign-body response to silicone implants.Nature biomedical engineering · 2025Article
- Identification of matrix stiffness-related molecular subtypes in HCC via integrating multi-omics analysis and machine learning algorithms.Journal of translational medicine · 2025Article
- Mechanoimmunological Control of Metastatic Site Selection.bioRxiv : the preprint server for biology · 2025Article
- Knocking Down HN1 Blocks Helicobacter pylori-Induced Malignant Phenotypes in Gastric Mucosal Cells and Inhibits Gastric Cancer Cell Proliferation, Cytoskeleton Remodeling, and Migration.Biochemical genetics · 2025Article
- Radiation-induced morphea of the breast - characterization and treatment of fibroblast dysfunction with repurposed mesalazine.Scientific reports · 2024Article
- The impact of matrix stiffness on hepatic cell function, liver fibrosis, and hepatocellular carcinoma-Based on quantitative data.Biophysics reviews · 2024Review
- Matrix stiffness-driven cancer progression and the targeted therapeutic strategy.Mechanobiology in medicine · 2023Review
- Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.Proteome science · 2023Article
- Tumor matrix stiffness provides fertile soil for cancer stem cells.Cancer cell international · 2023Review
- Mechanical Regulation of Mitochondrial Dynamics and Function in a 3D-Engineered Liver Tumor Microenvironment.ACS biomaterials science & engineering · 2023Article
- The Stiffness-Sensitive Transcriptome of Human Tendon Stromal Cells.Advanced healthcare materials · 2023Article
- Increased liver stiffness promotes hepatitis B progression by impairing innate immunity in CCl4-induced fibrotic HBVFrontiers in immunology · 2023Article
- Mechanical homeostasis imbalance in hepatic stellate cells activation and hepatic fibrosis.Frontiers in molecular biosciences · 2023Review
- Activation of Piezo1 contributes to matrix stiffness-induced angiogenesis in hepatocellular carcinoma.Cancer communications (London, England) · 2022Article
- Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion.International journal of molecular sciences · 2022Review
- Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors.Cancers · 2022Review
- Decellularized Colorectal Cancer Matrices as Bioactive Scaffolds for Studying Tumor-Stroma Interactions.Cancers · 2022Review
- Interplay between Cellular and Non-Cellular Components of the Tumour Microenvironment in Hepatocellular Carcinoma.Cancers · 2021Review
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased stromal stiffness is associated with hepatocellular carcinoma (HCC) development and progression. However, the molecular mechanism by which matrix stiffness stimuli modulate HCC progress is largely unknown. In this study, we explored whether matrix stiffness-mediated effects on osteopontin (OPN) expression occur in HCC cells. We used a previously reported in vitro culture system with tunable matrix stiffness and found that OPN expression was remarkably upregulated in HCC cells with increasing matrix stiffness. Furthermore, the phosphorylation level of GSK3β and the expression of nuclear β-catenin were also elevated, indicating that GSK3β/β-catenin pathway might be involved in OPN regulation. Knock-down analysis of integrin β1 showed that OPN expression and p-GSK3β level were downregulated in HCC cells grown on high stiffness substrate compared with controls. Simultaneously, inhibition of GSK-3β led to accumulation of β-catenin in the cytoplasm and its enhanced nuclear translocation, further triggered the rescue of OPN expression, suggesting that the integrin β1/GSK-3β/β-catenin pathway is specifically activated for matrix stiffness-mediated OPN upregulation in HCC cells. Tissue microarray analysis confirmed that OPN expression was positively correlated with the expression of LOX and COL1. Taken together, high matrix stiffness upregulated OPN expression in HCC cells via the integrin β1/GSK-3β/β-catenin signaling pathway. It highlights a new insight into a pathway involving physical mechanical signal and biochemical signal molecules which contributes to OPN expression in HCC cells.
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