ArticleBlood2016
Regulation of EBV LMP1-triggered EphA4 downregulation in EBV-associated B lymphoma and its impact on patients' survival.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.PLoS pathogens · 2025Article
- Combination of bortezomib and venetoclax targets the pro-survival function of LMP-1 and EBNA-3C of Epstein-Barr virus in spontaneous lymphoblastoid cell lines.PLoS pathogens · 2024Article
- Article
- FOXM1 promotes TGF-β2-induced injury of human lens epithelial cells by up regulating VEGFA expression.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2023Article
- Review
- High plasma EBV-DNA load and positive EBER status associated with viral recurrence and persistent infection in early treatment of lymphoma.Clinical and experimental medicine · 2023Article
- EBV-Mir-BART5-5p targets p53 independent pathway in cytoplasm: Potential role in EBV lymphomagenesis.Genes & diseases · 2023Article
- Mutations in latent membrane protein 1 of Epstein-Barr virus are associated with increased risk of posttransplant lymphoproliferative disorder in children.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023Article
- Ribonuclease 1 Enhances Antitumor Immunity against Breast Cancer by Boosting T cell Activation.International journal of biological sciences · 2023Article
- Protein-Protein Interaction Inhibitors Targeting the Eph-Ephrin System with a Focus on Amino Acid Conjugates of Bile Acids.Pharmaceuticals (Basel, Switzerland) · 2022Review
- High-Risk Human Papillomavirus and Epstein-Barr Virus Coinfection: A Potential Role in Head and Neck Carcinogenesis.Biology · 2021Review
- A cancer mutation promotes EphA4 oligomerization and signaling by altering the conformation of the SAM domain.The Journal of biological chemistry · 2021Article
- Eph receptors: the bridge linking host and virus.Cellular and molecular life sciences : CMLS · 2020Review
- Dysregulation of Dual-Specificity Phosphatases by Epstein-Barr Virus LMP1 and Its Impact on Lymphoblastoid Cell Line Survival.Journal of virology · 2020Article
- Emerging Roles for Eph Receptors and Ephrin Ligands in Immunity.Frontiers in immunology · 2019Review
- Comprehensive Molecular Profiling for Relapsed/Refractory Pediatric Burkitt Lymphomas-Retrospective Analysis of Three Real-Life Clinical Cases-Addressing Issues on Randomization and Customization at the Bedside.Frontiers in oncology · 2019Article
- Evaluation of latent membrane protein 1 and microRNA-155 for the prognostic prediction of diffuse large B cell lymphoma.Oncology letters · 2018Article
- Differential gene expression profiling linked to tumor progression of splenic marginal zone lymphoma.Scientific reports · 2017Article
- EBV, an inhibited receptor kinase, and lymphoma.Blood · 2016Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epstein-Barr virus (EBV), an oncogenic human virus, is associated with several lymphoproliferative disorders, including Burkitt lymphoma, Hodgkin disease, diffuse large B-cell lymphoma (DLBCL), and posttransplant lymphoproliferative disorder (PTLD). In vitro, EBV transforms primary B cells into lymphoblastoid cell lines (LCLs). Recently, several studies have shown that receptor tyrosine kinases (RTKs) play important roles in EBV-associated neoplasia. However, details of the involvement of RTKs in EBV-regulated B-cell neoplasia and malignancies remain largely unclear. Here, we found that erythropoietin-producing hepatocellular receptor A4 (EphA4), which belongs to the largest RTK Eph family, was downregulated in primary B cells post-EBV infection at the transcriptional and translational levels. Overexpression and knockdown experiments confirmed that EBV-encoded latent membrane protein 1 (LMP1) was responsible for this EphA4 suppression. Mechanistically, LMP1 triggered the extracellular signal-regulated kinase (ERK) pathway and promoted Sp1 to suppress EphA4 promoter activity. Functionally, overexpression of EphA4 prevented LCLs from proliferation. Pathologically, the expression of EphA4 was detected in EBV(-) tonsils but not in EBV(+) PTLD. In addition, an inverse correlation of EphA4 expression and EBV presence was verified by immunochemical staining of EBV(+) and EBV(-) DLBCL, suggesting EBV infection was associated with reduced EphA4 expression. Analysis of a public data set showed that lower EphA4 expression was correlated with a poor survival rate of DLBCL patients. Our findings provide a novel mechanism by which EphA4 can be regulated by an oncogenic LMP1 protein and explore its possible function in B cells. The results provide new insights into the role of EphA4 in EBV(+) PTLD and DLBCL.
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