ArticleOncotarget2017
Notch1 promotes vasculogenic mimicry in hepatocellular carcinoma by inducing EMT signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Breaking the bottlenecks in anti-tumor angiogenic therapy: targeting vasculogenic mimicry with natural products and traditional Chinese medicine.Frontiers in pharmacology · 2025Review
- Expression patterns and clinical significance of vasculogenic mimicry-related genes in patients with head and neck squamous cell carcinoma.Frontiers in immunology · 2025Article
- The role of kinesin superfamily proteins in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- ASPM stabilizes the NOTCH intracellular domain 1 and promotes oncogenesis by blocking FBXW7 binding in hepatocellular carcinoma cells.Molecular oncology · 2024Article
- Functional Enrichment Analysis of Tumor Microenvironment-Driven Molecular Alterations That Facilitate Epithelial-to-Mesenchymal Transition and Distant Metastasis.Bioinformatics and biology insights · 2024Article
- Lupeol and Paclitaxel cooperate in hindering hypoxia induced vasculogenic mimicry via suppression of HIF-1α-EphA2-Laminin-5γ2 network in human oral cancer.Journal of cell communication and signaling · 2023Article
- 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
- KIF2A participates in the progression of hepatocellular carcinoma and angiogenesis by interacting with Notch1.Experimental and therapeutic medicine · 2022Article
- Heme Oxygenase-1 Has a Greater Effect on Melanoma Stem Cell Properties Than the Expression of Melanoma-Initiating Cell Markers.International journal of molecular sciences · 2022Article
- Molecular mechanism of albumin in suppressing invasion and metastasis of hepatocellular carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2022Article
- Article
- Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment.Frontiers in oncology · 2022Review
- Review
- Article
- COE Inhibits Vasculogenic Mimicry by Targeting EphA2 in Hepatocellular Carcinoma, a Research Based on Proteomics Analysis.Frontiers in pharmacology · 2021Article
- VEGFC negatively regulates the growth and aggressiveness of medulloblastoma cells.Communications biology · 2020Article
- Thrombin is a therapeutic target for non-small-cell lung cancer to inhibit vasculogenic mimicry formation.Signal transduction and targeted therapy · 2020Article
- Vascular mimicry: changing the therapeutic paradigms in cancer.Molecular biology reports · 2020Review
- DJ‑1 promotes cell proliferation and tumor metastasis in esophageal squamous cell carcinoma via the Wnt/β‑catenin signaling pathway.International journal of oncology · 2020Article
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypervascularity is one of the main characteristics of hepatocellular carcinoma (HCC). However, the mechanisms of angiogenesis in HCC remain controversial. In this study, we investigate the role of Notch1 in angiogenesis of HCC. We found that Notch1 expression was correlated with formation of vasculogenic mimicry (VM) and expression of biomarkers of epithelial-to-mesenchymal transition (EMT) in the tumor specimens. Two HCC cell lines, HepG2 and MHCC97-H, with low and high Notch1 expression, respectively, were used to study the mechanism of VM formation both in vitro and in vivo. It was found that MHCC97-H cells, but not HepG2 cells form VM when they grow on matrigel in vitro. HepG2 cells gained the power of forming VM when they were overexpressed with Notch1, while knockdown Notch1 expression in MHCC97-H cells led to the loss of VM forming ability of the cells. Similar results were found in in vivo study. High expression of Notch1 in HepG2 promoted xenograft growth in nude mice, with abundant VM formation in the tumor samples. Moreover, we observed Notch1 was associated with the EMT and malignant behavior of hepatocellular carcinoma by analyzing clinical specimens, models for in vitro and in vivo experiments. HepG2 presented EMT phenomenon when induced by TGF-β1, accompanied by Notch1 activation while MHCC97-H with knockdown of Notch1 lost the responsiveness to TGF-β1 induction. Our results suggest that Notch1 promotes HCC progression through activating EMT pathway and forming VM. Our results will guide targeting Notch1 in new drug development.
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