ArticleJournal of hematology & oncology2019
Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis.
Article in Journal of hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 224 citations in OpenAlex.
- Piezo-type mechanosensitive ion channel component 1: a mechano-bioenergetic transducer in the tumour microenvironment.Annals of medicine · 2026Review
- Functional heterogeneity of exosomes in hepatocellular carcinoma (Review).Experimental and therapeutic medicine · 2026Review
- Mechanosensors Collaborate to Regulate DNA Damage Repair in Hepatocellular Carcinoma.Cancer research · 2026Article
- Decoding epithelial-mesenchymal transitions with multi-omics.Nature reviews. Genetics · 2026Review
- Matrix stiffness-induced YEATS2 drives HCC progression via epigenetic activation of the TGFBR2-TAZ-AKT pathway.Cell death and differentiation · 2026Article
- Defect-Engineered BiOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SNX8 regulates BMPR2-mediated SMAD5 proteostasis to drive epithelial-mesenchymal transition in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Artificial Intelligence-Based Body Composition Analysis Reveals Sex-Specific Prognostic Markers and Their Clinical Value in Gastric Cancer: A Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Matrix stiffness drives HCC invasion and metastasis via interfering with TRIM21-mediated SCD1 ubiquitination.Oncogene · 2026Article
- Matrix stiffness drives squamous cell carcinoma progression via a Piezo1-mediated mechanotransduction feedback loop.Journal of advanced research · 2026Article
- Matrix Stiffness Directs Stemness Signatures in Breast Cancer.Advanced healthcare materials · 2026Article
- Decoupling Mechanical Confinement and Fibrotic Extracellular Matrix Signaling in Vestibular Schwannoma Using Tunable 3D Hydrogels.Cellular and molecular bioengineering · 2026Article
- Hepatocyte-Derived S100A4/A6/A10/A11 Proteins Promote Liver Fibrosis by Direct and Indirect Activation of HSCs.Inflammation · 2026Article
- Cell Mechanics in Cancer: Integrating Mechanotransduction Pathways Within the Tumor Microenvironment.Journal of cellular physiology · 2026Review
- Article
- FNDC1 is closely related to poor prognosis and immune cell infiltration in gastric cancer.Scientific reports · 2026Article
- Acetyl-CoA synthase 1 mediates metabolic reprogramming to promote proliferation and metastasis of osteosarcoma.Journal of orthopaedic translation · 2026Article
- Deubiquitinase OTUD5 facilitates stiffness-induced hepatic stellate cell activation by stabilizing YAP.Molecular and cellular biochemistry · 2026Article
- Hyperglycemia in Diabetes Drives Hepatic Fibrosis Through the Non-Enzymatic Function of HK2 and AGEs-mediated Matrix Stiffening.International journal of biological sciences · 2026Article
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
70 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased liver stiffness exerts a detrimental role in driving hepatocellular carcinoma (HCC) malignancy and progression, and indicates a high risk of unfavorable outcomes. However, it remains largely unknown how liver matrix stiffness as an independent cue triggers epithelial-mesenchymal transition (EMT) and facilitates HCC metastasis.
methodsBuffalo rat HCC models with different liver stiffness backgrounds and an in vitro Col I-coated cell culture system with tunable stiffness were used in the study to explore the effects of matrix stiffness on EMT occurrence and its underlying molecular mechanism. Clinical significance of liver stiffness and key molecules required for stiffness-induced EMT were validated in HCC cohorts with different liver stiffness.
resultsHCC xenografts grown in higher stiffness liver exhibited worse malignant phenotypes and higher lung metastasis rate, suggesting that higher liver stiffness promotes HCC invasion and metastasis. Cell tests in vitro showed that higher matrix stiffness was able to strikingly strengthen malignant phenotypes and independently induce EMT occurrence in HCC cells, and three signaling pathways converging on Snail expression participated in stiffness-mediated effect on EMT including integrin-mediated S100A11 membrane translocation, eIF4E phosphorylation, and TGF β1 autocrine. Additionally, the key molecules required for stiffness-induced EMT were highly expressed in tumor tissues of HCC patients with higher liver stiffness and correlated with poor tumor differentiation and higher recurrence.
conclusionsHigher matrix stiffness as an initiator triggers epithelial-mesenchymal transition (EMT) in HCC cells independently, and three signaling pathways converging on Snail expression contribute to this pathological process. This work highlights a significant role of biomechanical signal in triggering EMT and facilitating HCC invasion and metastasis.
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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.