ArticleCell death & disease2021
Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 70 citations in OpenAlex.
- Matrix stiffness-induced YEATS2 drives HCC progression via epigenetic activation of the TGFBR2-TAZ-AKT pathway.Cell death and differentiation · 2026Article
- From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.Microorganisms · 2026Review
- Matrix stiffness may drive multi-cellular crosstalk via YAP signaling in biliary atresia liver fibrosis: a mechanistic review.Frontiers in cell and developmental biology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Taohong Siwu Decoction relieves renal fibrosis: based on network pharmacology and experimental confirmation.Renal failure · 2025Article
- Characterizing Kupffer Cell Production of CD5 Antigen-Like and Its Function on Regulating Migration of Natural Killer T Cells.The American journal of pathology · 2025Article
- Stiffness-activated hepatic stellate cells boost HCC migration via TGM2/ITGB1-mediated matrix remodeling and mitochondrial transfer.JHEP reports : innovation in hepatology · 2025Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Liver cancer-specific prognostic model developed using endoplasmic reticulum stress-related LncRNAs and LINC01011 as a potential therapeutic target.BMC medical genomics · 2025Article
- Forcing the code: tension modulates signaling to drive morphogenesis and malignancy.Genes & development · 2025Review
- Knowledge landscape of macrophage research in liver fibrosis: a bibliometric review of the literature from WoSCC.Frontiers in pharmacology · 2025Review
- Challenges ofFrontiers in cell and developmental biology · 2025Review
- Sinusoidal communication in chronic liver disease.Clinical and molecular hepatology · 2025Review
- The impact of ICOSL/ICOS pathway-regulated long non-coding RNAs on liver fibrosis in mice infected with Schistosoma japonicum.Parasites & vectors · 2024Article
- Role of Emerin in regulating fibroblast differentiation and migration at the substrate of stiffness coupled topology.Acta biochimica et biophysica Sinica · 2024Article
- Redox signaling-mediated tumor extracellular matrix remodeling: pleiotropic regulatory mechanisms.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Combinatorial Microgels for 3D ECM Screening and Heterogeneous Microenvironmental Culture of Primary Human Hepatic Stellate Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Bioelectricity in dental medicine: a narrative review.Biomedical engineering online · 2024Review
- Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.Scientific reports · 2024Article
- The C-type lectin COLEC10 is predominantly produced by hepatic stellate cells and involved in the pathogenesis of liver fibrosis.Cell death & disease · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatic stellate cells (HSCs) activation by myofibroblastic differentiation is critical for liver fibrosis. Crosstalk between stromal cells and tumor cells in the microenvironment alters the properties and facilitates the growth and metastasis of tumor cells. How mechanical stimuli originally stiffness of extracellular matrix (ECM) contribute to tumor development remains poorly understood. Here, we demonstrated that stiffness contributes to mechanosignal transduction in HSCs, which promotes hepatocellular carcinoma (HCC) cells growth and metastasis through secretion of FGF2. On stiffness matrix, HSCs activation was confirmed by immunofluorescence (IF) and Western blot (WB) for α-smooth muscle actin (SMA). Increasing matrix stiffness promoted HSCs activation by CD36-AKT-E2F3 mechanosignaling through shRNA-mediated E2F3 knockdown, AKT inhibitors, and CD36 shRNA. Moreover, ChIP-qPCR. Confirmed that E2F3 combined the promoter of FGF2, and stiffness promoted FGF2 expression. On a stiff matrix, HCC cells cultured with conditioned media (CM) from HSCs increased HCC cells growth and metastasis by binding FGFR1 to activate PI3K/AKT and MEK/ERK signaling pathways. Moreover, conditional E2F3 knockout mice were subjected to CCl4 treatment to assess the role of E2F3 in HSC activation. Additionally, the DEN-induced HCC model was also used to evaluate the role of E2F3 in liver fibrosis and HCC growth. In conclusion, we demonstrated that stiffness-induced HSC activation by E2F3 dependent. Stiffness activated CD36-AKT-E2F3 signaling and targeted FGF2 transcription, subsequently, activated HCC growth and metastasis by FGFR1-mediated PI3K/AKT and MEK/ERK signaling.
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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.