ArticlePloS one2012
Heparin inhibits Hepatocyte Growth Factor induced motility and invasion of hepatocellular carcinoma cells through early growth response protein 1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Exploring the Lung-Liver Axis in Pulmonary Arterial Hypertension.Comprehensive Physiology · 2026Article
- A Novel Zebrafish Liver-Specific Metastasis Model Reveals c-Met as a Driver of Liver Tropism.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- EGR1 suppresses HCC growth and aerobic glycolysis by transcriptionally downregulating PFKL.Journal of experimental & clinical cancer research : CR · 2024Article
- Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.Chinese medicine · 2023Article
- Article
- Dexmedetomidine promotes apoptosis and suppresses proliferation of hepatocellular carcinoma cells via microRNA-130a/EGR1 axis.Cell death discovery · 2022Article
- High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells.Scientific reports · 2021Article
- Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1.Aging · 2020Article
- Comparison of the Interactions of Different Growth Factors and Glycosaminoglycans.Molecules (Basel, Switzerland) · 2019Article
- Protease Nexin I is a feedback regulator of EGF/PKC/MAPK/EGR1 signaling in breast cancer cells metastasis and stemness.Cell death & disease · 2019Article
- Article
- Induction of early growth response gene 1 (EGR1) by endoplasmic reticulum stress is mediated by the extracellular regulated kinase (ERK) arm of the MAPK pathways.Biochimica et biophysica acta. Molecular cell research · 2019Article
- CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma.OncoTargets and therapy · 2019Article
- REC8 inhibits EMT by downregulating EGR1 in gastric cancer cells.Oncology reports · 2018Article
- Pleiotropic Effects of Heparins: From Clinical Applications to Molecular Mechanisms in Hepatocellular Carcinoma.Canadian journal of gastroenterology & hepatology · 2018Review
- Attenuation of MET-mediated migration and invasion in hepatocellular carcinoma cells by SOCS1.World journal of gastroenterology · 2017Article
- Signaling Pathways as Potential Therapeutic Targets in Hepatocarcinogenesis.Journal of gastrointestinal cancer · 2017Review
- Expression and clinical significance of EGR-1 and PTEN in the pituitary tumors of elderly patients.Oncology letters · 2017Article
- The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.Journal of cell communication and signaling · 2017Article
- Elevated hepatocyte growth factor expression as an autocrine c-Met activation mechanism in acquired resistance to sorafenib in hepatocellular carcinoma cells.Cancer science · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The Hepatocyte Growth Factor (HGF)/c-Met signaling pathway regulates hepatocyte proliferation, and pathway aberrations are implicated in the invasive and metastatic behaviors of hepatocellular carcinoma (HCC). In addition to c-Met, heparin acts as a co-receptor to modulate pathway activity. Recently, anti-metastatic and anti-cancer effects of heparin have been reported. However, the role of heparin in the regulation of HGF signaling remains controversial and the effects of heparin on HGF-induced biological responses during hepatocarcinogenesis is not yet defined. In this study we determined the effects of heparin on HGF-induced activities of HCC cells and the underlying molecular mechanisms. Here, we report for the first time that heparin inhibits HGF-induced adhesion, motility and invasion of HCC cells. In addition, heparin reduced HGF-induced activation of c-Met and MAPK in a dose-dependent manner, as well as decreased transcriptional activation and expression of Early growth response factor 1 (Egr1). HGF-induced MMP-2 and MMP-9 activation, and MT1-MMP expression, also were inhibited by heparin. Stable knockdown of Egr1 caused a significant decrease in HGF-induced invasion, as well as the activation and expression of MMPs. Parallel to these findings, the overexpression of Egr1 increased the invasiveness of HCC cells. Our results suggest that Egr1 activates HGF-induced cell invasion through the regulation of MMPs in HCC cells and heparin inhibits HGF-induced cellular invasion via the downregulation of Egr1. Therefore, heparin treatment might be a therapeutic approach to inhibit invasion and metastasis of HCC, especially for patients with active HGF/c-Met signaling.
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