ArticleThe American journal of pathology2020
Phosphorylated Ezrin (Thr567) Regulates Hippo Pathway and Yes-Associated Protein (Yap) in Liver.
Article in The American journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets.Molecular biology reports · 2024Review
- Changes in the expression profile of serum lncRNAs in pregnant women with high hepatitis B viral load during antiviral and non-antiviral treatment.BMC pregnancy and childbirth · 2024Article
- Celastrol alleviates atopic dermatitis by regulating Ezrin-mediated mitochondrial fission and fusion.Journal of cellular and molecular medicine · 2024Article
- Review
- Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications.Frontiers in cell and developmental biology · 2023Review
- Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway.Open life sciences · 2023Article
- The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases.Heliyon · 2022Review
- Downregulation of CDC42 inhibits the proliferation and stemness of human trophoblast stem cell via EZRIN/YAP inactivation.Cell and tissue research · 2022Article
- Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin.International journal of molecular sciences · 2022Review
- Advances in prognostic and therapeutic targets for hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The hippo signaling pathway.Frontiers in oncology · 2022Review
- Liver regeneration biology: Implications for liver tumour therapies.World journal of clinical oncology · 2021Review
- CD81 marks immature and dedifferentiated pancreatic β-cells.Molecular metabolism · 2021Article
- SEPT6 drives hepatocellular carcinoma cell proliferation, migration and invasion via the Hippo/YAP signaling pathway.International journal of oncology · 2021Observational
- Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions.Biomolecules · 2021Article
- Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The activation of CD81 [the portal of entry of hepatitis C virus (HCV)] by agonistic antibody results in phosphorylation of Ezrin via Syk kinase and is associated with inactivation of the Hippo pathway and increase in yes-associated protein (Yap1). The opposite occurs when glypican-3 or E2 protein of HCV binds to CD81. Hepatocyte-specific glypican-3 transgenic mice have decreased levels of phosphorylated (p)-Ezrin (Thr567) and Yap, increased Hippo activity, and suppressed liver regeneration. The role of Ezrin in these processes has been speculated, but not proved. We show that Ezrin has a direct role in the regulation of Hippo pathway and Yap. Forced expression of plasmids expressing mutant Ezrin (T567D) that mimics p-Ezrin (Thr567) suppressed Hippo activity and activated Yap signaling in hepatocytes in vivo and enhanced activation of pathways of β-catenin and leucine rich repeat containing G protein-coupled receptor 4 (LGR4) and LGR5 receptors. Hepatoma cell lines JM1 and JM2 have decreased CD81 expression and Hippo activity and up-regulated p-Ezrin (T567). NSC668394, a p-Ezrin (Thr567) antagonist, significantly decreased hepatoma cell proliferation. We additionally show that p-Ezrin (T567) is controlled by epidermal growth factor receptor and MET. Ezrin phosphorylation, mediated by CD81-associated Syk kinase, is directly involved in regulation of Hippo pathway, Yap levels, and growth of normal and neoplastic hepatocytes. The finding has mechanistic and potentially therapeutic applications in hepatocyte growth biology, hepatocellular carcinoma, and HCV pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.