ArticleJournal of experimental & clinical cancer research : CR2022
HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study.Nature communications · 2026Trial
- Nilotinib induces immunogenic cuproptosis to potentiate cancer immunotherapy.Cell reports. Medicine · 2026Article
- Article
- m6A methylation-modified ETV1 drives multiple myeloma progression and M2 polarization of tumor-associated macrophage through transcriptional activation of RBMS1.Journal of translational medicine · 2026Article
- ETV1 Drives CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.International journal of surgery (London, England) · 2026Article
- Polymeric Nanomedicines for siRNA Delivery in Hepatocellular Carcinoma: Emerging Therapeutic Strategies, Combination Approaches, and Translational Perspectives.International journal of nanomedicine · 2026Review
- Fe-MOF loaded with capmatinib to reverse immunosuppressive microenvironment and inhibit tumor metastasis after radiofrequency ablation.Journal of nanobiotechnology · 2025Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- Interaction of neuropilin-1 and hepatocyte growth factor/C-Met pathway in liver fibrosis progression in hepatocyte-specific NRP-1 knockout mice.Journal of gastroenterology · 2025Article
- PEA3 Transcription Factors, Role in Invasion, Proliferation and Radioresistance of Glioblastoma Stem Cells.Journal of cellular and molecular medicine · 2025Article
- SUMO modified ETV1 promotes M2-polarized tumor-associated macrophage infiltration and cancer progression by facilitating CCL2 transcription in esophageal squamous cell carcinoma cells.Cancer immunology, immunotherapy : CII · 2025Article
- Functional interaction between receptor tyrosine kinase MET and ETS transcription factors promotes prostate cancer progression.Molecular oncology · 2025Article
- ETS-1 in tumor immunology: implications for novel anti-cancer strategies.Frontiers in immunology · 2025Review
- Advances in Lipid-Based Nanomedicine: Pathway Specific siRNA Therapy and Optimizing Delivery for Hepatocellular Carcinoma.International journal of nanomedicine · 2025Review
- Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway.Frontiers in cardiovascular medicine · 2025Article
- Pan-cancer analysis of the potential of PEA3 subfamily genes as tumor markers.Scientific reports · 2024Article
- Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.Global medical genetics · 2024Review
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Pre-metastatic niche: formation, characteristics and therapeutic implication.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMetastasis is a major determinant of death in patients with hepatocellular carcinoma (HCC). Dissecting key molecular mediators that promote this malignant feature may help yield novel therapeutic insights. Here, we investigated the role of E-twenty-six transformation-specific variant 1 (ETV1), a member of the E-twenty-six transformation-specific (ETS) family, in HCC metastasis.
methodsThe clinical significance of ETV1 and its target genes in two independent cohorts of HCC patients who underwent curative resection were assessed by Kaplan-Meier analysis and Multivariate Cox proportional hazards model. Luciferase reporter assay and chromatin immunoprecipitation assay were used to detect the transcriptional regulation of target gene promoters by ETV1. The effect of ETV1 on invasiveness and metastasis of HCC were detected by transwell assays and the orthotopically metastatic model.
resultsETV1 expression was frequently elevated in human HCC specimens. Increased ETV1 expression was associated with the malignant biological characteristics and poor prognosis of HCC patients. ETV1 facilitated invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ETV1 promoted HCC metastasis via upregulating metastasis-related genes, including protein tyrosine kinase 2 (PTK2) and MET. Down-regulated the expression of PTK2 or tyrosine protein kinase Met (c-MET) decreased ETV1-mediated HCC metastasis. Hepatocyte growth factor (HGF) upregulated ETV1 expression through activating c-MET-ERK1/2-ELK1 pathway. Notably, in two independent cohorts, patients with positive coexpression of ETV1/PTK2 or ETV1/c-MET had worse prognosis. Furthermore, the combination of PTK2 inhibitor defactinib and c-MET inhibitor capmatinib significantly suppressed HCC metastasis induced by ETV1.
conclusionThis study uncovers functional and prognostic roles for ETV1 in HCC and exposes a positive feedback loop of HGF-ERK1/2-ETV1-c-MET. Targeting this pathway may provide a potential therapeutic intervention for ETV1-overexpressing HCC.
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