ArticleCell communication and signaling : CCS2023
Hepatocellular carcinoma cells remodel the pro-metastatic tumour microenvironment through recruitment and activation of fibroblasts via paracrine Egfl7 signaling.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 14 citations in OpenAlex.
- TERT drives liver tumorigenesis beyond telomere elongation.Life science alliance · 2026Article
- EGFL7 Inhibits the Immune Response in Metastatic Castration-Resistant Prostate Cancer by Deactivating Endothelial Intercellular Adhesion Molecule-1.The world journal of men's health · 2026Article
- Hepatic Stellate Cell-Specific METTL3 Deficiency Promotes Hepatocellular Carcinoma Progression via BMP10-SMAD1/5/8 Signaling.Cancer research communications · 2026Article
- Saikosaponin D and paeoniflorin improve the HCC immune microenvironment via CLCF1/PD-L1 mediated crosstalk between CAFs and tumor cells.Scientific reports · 2026Article
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Immune escape in portal vein tumor thrombus: an intravascular tumor-immune niche framework for hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Stiffness-activated hepatic stellate cells boost HCC migration via TGM2/ITGB1-mediated matrix remodeling and mitochondrial transfer.JHEP reports : innovation in hepatology · 2025Article
- EGFL9 regulates the growth and metastasis of hepatocellular carcinoma through EGFR/PI3K/AKT signaling pathway and amino acid modulation.Discover oncology · 2025Article
- CAF-derived exosomes drive the FGF4/SHH feedback loop by encapsulating GREM1 in non-small cell lung cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Targeting B4GALT3 in BMSCs-EVs for Therapeutic Control of HCC via NF-κB pathway inhibition.Cell biology and toxicology · 2025Article
- Development of a Novel four-gene Model for Monitoring the Progression from Metabolic Dysfunction-associated Steatotic Liver Disease to Hepatocellular Carcinoma in Males.Journal of Cancer · 2025Article
- Periostin-integrin signaling in hepatocellular carcinoma: from biological function to clinical application.Frontiers in cell and developmental biology · 2025Review
- The relationship between the tumor microenvironment of hepatocellular carcinoma - including cancer-associated fibroblasts and tumor-associated macrophages - and apparent diffusion coefficient.American journal of cancer research · 2025Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe tumour microenvironment consists of a complex and dynamic milieu of cancer cells, including tumour-associated stromal cells (leukocytes, fibroblasts, vascular cells, etc.) and their extracellular products. During invasion and metastasis, cancer cells actively remodel the tumour microenvironment and alterations of microenvironment, particularly cancer-associated fibroblasts (CAFs), can promote tumour progression. However, the underlying mechanisms of the CAF formation and their metastasis-promoting functions remain unclear.
methodsPrimary liver fibroblasts and CAFs were isolated and characterized. CAFs in clinical samples were identified by immunohistochemical staining and the clinical significance of CAFs was also analysed in two independent cohorts. A transwell coculture system was used to confirm the role of HCC cells in CAF recruitment and activation. qRT-PCR, western blotting and ELISA were used to screen paracrine cytokines. The role and mechanism of Egfl7 in CAFs were explored via an in vitro coculture system and an in vivo mouse orthotopic transplantation model.
resultsWe showed that CAFs in hepatocellular carcinoma (HCC) are characterized by the expression of α-SMA and that HCC cells can recruit liver fibroblasts (LFs) and activate them to promote their transformation into CAFs. High α-SMA expression, indicating high CAF infiltration, was correlated with malignant characteristics. It was also an independent risk factor for HCC survival and could predict a poor prognosis in HCC patients. Then, we demonstrated that EGF-like domain multiple 7 (Egfl7) was preferentially secreted by HCC cells, and exhibited high potential to recruit and activate LFs into the CAF phenotype. The ability of Egfl7 to modulate LFs relies upon increased phosphorylation of FAK and AKT via the receptor α
conclusionOur data highlighted a novel role of Egfl7 in remodelling the tumour microenvironment: it recruits LFs and activates them to promote their transformation into CAFs via the α
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