ArticleBMC cancer2021
Inhibition of matrix stiffness relating integrin β1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Nanomedicine targeting ECM stiffness: restoring mechanical homeostasis for cancer immunotherapy.Materials today. Bio · 2026Review
- Structural architecture of collagen and collagen-fibronectin networks is associated with the invasive behavior of liver cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- TRIM29 suppresses malignant progression in lung squamous cell carcinoma by shaping an immunosuppressive tumor microenvironment.Scientific reports · 2026Article
- Photocrosslinkable lung dECM hydrogels promote stiffness-dependent lung cancer growth and chemoresistance.Materials today. Bio · 2026Article
- Integrins in cancer: insights into mechanisms and therapeutic potential.Cell communication and signaling : CCS · 2026Review
- Matrix type influences embedded patient-derived osteosarcoma organoid invasion and response to treatment.Frontiers in pharmacology · 2026Article
- Review
- FN9-10ELP, an ECM-Mimetic Fusion Protein, Protects Human Mesenchymal Stem Cells from Etoposide-Induced Senescence.International journal of molecular sciences · 2025Article
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
- Tumor-infiltrating immune cells state-implications for various breast cancer subtypes.Frontiers in immunology · 2025Review
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
- MAPK/ERK Signaling in Tumorigenesis: mechanisms of growth, invasion, and angiogenesis.EXCLI journal · 2025Review
- The role of liver cancer stem cells in hepatocellular carcinoma metastasis.Cancer biology & therapy · 2024Review
- The impact of matrix stiffness on hepatic cell function, liver fibrosis, and hepatocellular carcinoma-Based on quantitative data.Biophysics reviews · 2024Review
- Unveiling the Role of Mechanical Microenvironment in Hepatocellular Carcinoma: Molecular Mechanisms and Implications for Therapeutic Strategies.International journal of biological sciences · 2024Review
- Functional Roles of CD133: More than Stemness Associated Factor Regulated by the Microenvironment.Stem cell reviews and reports · 2024Review
- Cancer stem cells and their niche in cancer progression and therapy.Cancer cell international · 2023Review
- Targeting the mechano-microenvironment and liver cancer stem cells: a promising therapeutic strategy for liver cancer.Cancer biology & medicine · 2023Review
- YAP at the Crossroads of Biomechanics and Drug Resistance in Human Cancer.International journal of molecular sciences · 2023Review
- Tumor matrix stiffness provides fertile soil for cancer stem cells.Cancer cell international · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development.
methodsThe matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin β1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors.
resultsOur study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin β1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin β1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts.
conclusionA higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin β1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.