ArticleCell communication and signaling : CCS2014
The tumor marker Fascin is induced by the Epstein-Barr virus-encoded oncoprotein LMP1 via NF-κB in lymphocytes and contributes to their invasive migration.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
- Autoimmune disease-associated lymphomas: research progress and review.Frontiers in immunology · 2025Review
- Versatile function of NF-ĸB in inflammation and cancer.Experimental hematology & oncology · 2024Review
- Kinases and therapeutics in pathogen mediated gastric cancer.Molecular biology reports · 2022Review
- Article
- Fascin-1: Updated biological functions and therapeutic implications in cancer biology.BBA advances · 2022Review
- Review
- The FDA-Approved Antiviral Raltegravir Inhibits Fascin1-Dependent Invasion of Colorectal Tumor Cells In Vitro and In Vivo.Cancers · 2021Article
- Transfer of HTLV-1 p8 and Gag to target T-cells depends on VASP, a novel interaction partner of p8.PLoS pathogens · 2020Article
- Quantitating the Transfer of the HTLV-1 p8 Protein Between T-Cells by Flow Cytometry.Frontiers in microbiology · 2018Article
- Role of microRNAs and Exosomes inFrontiers in microbiology · 2018Review
- Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.Oncogenesis · 2017Article
- Epstein-Barr virus and its association with Fascin expression in colorectal cancers in the Syrian population: A tissue microarray study.Human vaccines & immunotherapeutics · 2017Article
- The Tax-Inducible Actin-Bundling Protein Fascin Is Crucial for Release and Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 (HTLV-1).PLoS pathogens · 2016Article
- Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers.Trends in microbiology · 2016Review
- p53 controls colorectal cancer cell invasion by inhibiting the NF-κB-mediated activation of Fascin.Oncotarget · 2015Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe actin-bundling protein Fascin (FSCN1) is a tumor marker that is highly expressed in numerous types of cancer including lymphomas and is important for migration and metastasis of tumor cells. Fascin has also been detected in B lymphocytes that are freshly-infected with Epstein-Barr virus (EBV), however, both the inducers and the mechanisms of Fascin upregulation are still unclear.
resultsHere we show that the EBV-encoded oncoprotein latent membrane protein 1 (LMP1), a potent regulator of cellular signaling and transformation, is sufficient to induce both Fascin mRNA and protein in lymphocytes. Fascin expression is mainly regulated by LMP1 via the C-terminal activation region 2 (CTAR2). Block of canonical NF-κB signaling using a chemical inhibitor of IκB kinase β (IKKβ) or cotransfection of a dominant-negative inhibitor of IκBα (NFKBIA) reduced not only expression of p100, a classical target of the canonical NF-κB-pathway, but also LMP1-induced Fascin expression. Furthermore, chemical inhibition of IKKβ reduced both Fascin mRNA and protein levels in EBV-transformed lymphoblastoid cell lines, indicating that canonical NF-κB signaling is required for LMP1-mediated regulation of Fascin both in transfected and transformed lymphocytes. Beyond that, chemical inhibition of IKKβ significantly reduced invasive migration of EBV-transformed lymphoblastoid cells through extracellular matrix. Transient transfection experiments revealed that Fascin contributed to LMP1-mediated enhancement of invasive migration through extracellular matrix. While LMP1 enhanced the number of invaded cells, functional knockdown of Fascin by two different small hairpin RNAs resulted in significant reduction of invaded, non-attached cells.
conclusionsThus, our data show that LMP1-mediated upregulation of Fascin depends on NF-κB and both NF-κB and Fascin contribute to invasive migration of LMP1-expressing lymphocytes.
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