title: Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma.
abstract: Undifferentiated nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignant tumor. A consistent elevation in EBV antibody titers is a well-established risk factor for the development of NPC. The pathophysiological relationship and molecular mechanisms of EBV-mediated carcinogenesis have not been fully elucidated. While NPC tumors are known to express three EBV-encoded proteins, EBNA1, LMP1, and LMP2, they also express a large number of virus-encoded small RNAs (EBERs) and microRNAs (miRNAs). Among them, LMP1 may be a central player in the development of NPC. LMP1, an EBV-encoded primary oncogene, functions as a viral mimic of the TNFR family member, CD40, and engages in a number of signaling pathways that induce morphological and phenotypic alterations in epithelial cells. LMP1 upregulates EMT, and contributes to the highly metastatic features of NPC. Moreover, LMP1-associated EMT is accompanied by the expression of cancer stem cell (CSC)/cancer progenitor cell (CPC) markers (CD44high/CD24low) and the acquisition of stem cell/progenitor cell-like properties. BART miRNAs, encoded from the BamHI-A region of the viral genome, are the most abundant transcripts. They modulate apoptosis and host innate immune defense mechanisms. Some BART1 miRNAs are considered to negatively regulate LMP1 protein expression. LMP1 is secreted via exosomes, is incorporated into EBV-uninfected cells by endocytosis, and affects the environment surrounding the tumor. Here we reviewed the contribution of EBV gene products to NPC pathogenesis in relation with LMP1.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8640, Japan. tomoy@med.kanazawa-u.ac.jp
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Nakanishi
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
mesh_terms: D058750:Epithelial-Mesenchymal Transition; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D042583:Lymphangiogenesis; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology / Q000821:virology; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000209:etiology; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins
keywords: Cancer stem cell; EMT; Epstein–Barr virus; LMP1; Nasopharyngeal carcinoma