ArticlePloS one2013
Epigenetic upregulation of HGF and c-Met drives metastasis in hepatocellular carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Somatostatin Effect on Growth Factors in Hepatocellular Carcinoma.Current issues in molecular biology · 2026Article
- Decoding Hepatocellular Carcinoma Metastasis: Molecular Mechanisms, Targeted Therapies, and Potential Biomarkers.Current issues in molecular biology · 2025Review
- Bioactive Products Targeting C-Met As Potential Antitumour Drugs.Anti-cancer agents in medicinal chemistry · 2025Review
- HGF/c-MET axis contributes to CLL cell survival by regulating multiple mechanisms making it a potential therapeutic target for CLL treatment.Frontiers in pharmacology · 2025Article
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Role of p53 suppression in the pathogenesis of hepatocellular carcinoma.World journal of gastrointestinal pathophysiology · 2023Review
- DNA Methylation Dynamics During Esophageal Epithelial Regeneration Following Repair with Acellular Silk Fibroin Grafts in Rat.Advanced biology · 2023Article
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
- The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.Endocrine-related cancer · 2022Review
- Different Inhibition of Nrf2 by Two Keap1 Isoforms α and β to Shape Malignant Behaviour of Human Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- Function of the Long Noncoding RNAs in Hepatocellular Carcinoma: Classification, Molecular Mechanisms, and Significant Therapeutic Potentials.Bioengineering (Basel, Switzerland) · 2022Review
- Circulating tumour cells in the -omics era: how far are we from achieving the 'singularity'?British journal of cancer · 2022Review
- Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.Molecular cancer · 2022Review
- The role of tumor microenvironment reprogramming in primary liver cancer chemotherapy resistance.Frontiers in oncology · 2022Review
- Molecular classification of hepatocellular carcinoma: prognostic importance and clinical applications.Journal of cancer research and clinical oncology · 2022Review
- Dependence receptors: new targets for cancer therapy.EMBO molecular medicine · 2021Review
- Single-cell DNA methylome analysis of circulating tumor cells.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2021Article
- Single-cell transcriptomic analysis in a mouse model deciphers cell transition states in the multistep development of esophageal cancer.Nature communications · 2020Article
- Thiosemicarbazones suppress expression of the c-Met oncogene by mechanisms involving lysosomal degradation and intracellular shedding.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Hepatocyte growth factor (HGF) and its receptor, c-Met, are important regulators of growth and differentiation of healthy hepatocytes. However, upregulation of HGF and c-Met have been associated with tumor progression and metastasis in hepatocellular carcinoma (HCC). Hematogenous dissemination is the most common route for cancer metastasis, but the role of HGF and c-Met in circulating tumor cells (CTCs) is unknown. We have isolated and established a circulating tumor cell line from the peripheral blood of a mouse HCC model. Our studies show that these CTCs have increased expression of HGF and c-Met in comparison to the primary tumor cells. The CTCs display phenotypic evidence of epithelial-mesenchymal transition (EMT) and the EMT appears to be inducible by HGF. Epigenetic analysis of the c-Met promoter identified significant loss of DNA methylation in CTCs which correlated with overexpression of c-Met and increased expression of HGF. Six specific CpG sites of c-Met promoter demethylation were identified. CTCs show significantly increased tumorigenicity and metastatic potential in a novel orthotopic syngeneic model of metastatic HCC. We conclude that during hematogenous dissemination in HCC, CTCs undergo EMT under the influence of increased HGF. This process also involves up regulation of c-Met via promoter demethylation at 6 CpG sites. Consequently, targeting HGF and c-Met expression by CTCs may be a novel non-invasive approach with potential clinical applications in HCC management.
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