Promotion of metastasis in nasopharyngeal carcinoma by Epstein-Barr virus latent membrane protein-1.
Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV). Latent membrane protein-1 (LMP-1) is an EBV-encoded oncoprotein and is detected in approximately 50-70% of patients with NPC. LMP-1 is thought to play an essential role in tumorigenesis of NPC. In addition to its transforming properties, LMP-1 has been suggested to be associated with promotion of metastasis. Metastasis is a phenomenon composed of multiple sequential cascades. Reduction of tumor cell adhesion, degradation of extracellular matrix, basement membrane, enhancement of cell motility, and promotion of neovascularization are thought to be essential steps. LMP-1 down-regulates expression of E-cadherin, induces matrix metalloproteinase-9 and urokinase type-plasminogen activator through activation of NF-kappaB and AP-1, and enhances cell motility via ets-1 activation. LMP-1 also induces vascular endothelial growth factor through cyclooxygenase-2 activation and interleukin-8 through NF-kappaB activation. Clinical studies suggested the association of these factors with metastatic status of patients with NPC. In this review, the role of LMP-1 in the metastasis of NPC is discussed.
Yoshizaki
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Otolaryngology, Graduate School of Medicine Kanazawa University, Takaramachi, Japan.
D015820:Cadherins / Q000096:biosynthesis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D051546:Cyclooxygenase 2; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008565:Membrane Proteins; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D017434:Protein Structure, Tertiary; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D050783:Proto-Oncogene Proteins c-ets; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000502:physiology*
D015820:Cadherins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C494041:ETS1 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014763:Viral Matrix Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D019859:Proto-Oncogene Proteins c-met; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9