Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion.
Decoy receptor 3 (DcR3), a member of tumor necrosis factor receptor superfamily, has been implicated in tumorigenesis through its abilities to modulate immune responses and induce angiogenesis. Epstein-Barr virus (EBV), a ubiquitous gamma-herpesvirus, is associated with malignancies including nasopharyngeal carcinoma (NPC). Previous studies show that DcR3 is overexpressed in EBV-positive lymphomas and Rta, an EBV transcription activator, can upregulate DcR3 in Burkitt lymphoma cell lines. However, DcR3 expression has not been demonstrated in EBV-associated NPC nor have there been any EBV latent genes linked to DcR3 upregulation. Here, we showed DcR3 was overexpressed in NPC. Higher DcR3 expression score and DcR3-positive rate were found in metastatic NPC than in primary NPC tissues, suggesting DcR3 may enhance cell metastatic potential. This hypothesis is supported by our observation that NPC HONE-1 cells overexpressing DcR3 exhibited significant higher migration and invasion abilities in vitro. We found besides Rta, EBV latent membrane protein (LMP) 1 can upregulate DcR3 via nuclear factor-kappaB and phosphatidylinositol 3-kinase-signaling events. Approximate 75% of LMP1-positive NPC tissues overexpressed DcR3, suggesting LMP1 may enhance DcR3 expression in vivo. Data herein suggested that increasing DcR3 expression by LMP1 not only helps EBV-associated cancer cells gain survival advantage by preventing host immune detection but also increases the chance of cancer metastasis by enhancing cell migration and invasion. All these DcR3-mediated events facilitate normal cells to gain cancer hallmarks.
Ho
Cheng-Hsun
CH
Institute of Microbiology and Immunology, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 112, Taiwan.
Chen
Chi-Long
CL
Li
Wing-Yin
WY
Chen
Chi-Ju
CJ
D015153:Blotting, Western; D002465:Cell Movement; D047369:Chromatin Immunoprecipitation; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005786:Gene Expression Regulation / Q000502:physiology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000502:physiology*; D017735:Virus Latency
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D012333:RNA, Messenger; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D014763:Viral Matrix Proteins; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases