Decoy receptor 3, upregulated by Epstein-Barr virus latent membrane protein 1, enhances nasopharyngeal carcinoma cell migration and invasion

• Published in: Carcinogenesis (New York) Vol. 30; no. 8; pp. 1443 - 1451
• Main Authors: Ho, Cheng-Hsun, Chen, Chi-Long, Li, Wing-Yin, Chen, Chi-Ju
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2009; Oxford Publishing Limited (England)
• Subjects: Biological and medical sciences; Blotting, Western; Carcinogenesis, carcinogens and anticarcinogens; Cell Movement; Chromatin Immunoprecipitation; Enzyme-Linked Immunosorbent Assay; Epstein-Barr virus; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - pathology; Epstein-Barr Virus Infections - virology; Gene Expression Regulation - physiology; Herpesvirus 4, Human - physiology; Humans; Immunoenzyme Techniques; Infectious diseases; Luciferases - metabolism; Medical sciences; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - virology; Neoplasm Invasiveness; NF-kappa B - genetics; NF-kappa B - metabolism; Otorhinolaryngology. Stomatology; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Receptors, Tumor Necrosis Factor, Member 6b - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Tumors; Up-Regulation; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Viral diseases; Viral Matrix Proteins - physiology; Virus Latency; Gammaherpesvirinae; Nasopharynx cancer; Herpesviridae; Decoy receptor 3; Epstein Barr virus; Malignant tumor; Nasopharynx carcinoma; Metastasis; Invasion; Infection; Virus; Cell motility; Viral disease; ENT disease; Pharynx disease; Cell migration; Cancer; Latent membrane protein 1
• DOI: 10.1093/carcin/bgp135
• ISSN: 0143-3334; 1460-2180

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 γ-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.