title: Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers.
abstract: Cancer progression begins when malignant cells colonize adjacent sites, and it is characterized by increasing tumor heterogeneity, invasion and dissemination of cancer cells. Clinically, progression is the most relevant stage in the natural history of cancers. A given virus is usually regarded as oncogenic because of its ability to induce malignant transformation of cells. Nonetheless, oncogenic viruses may also be important for the progression of infection-associated cancers. Recently this hypothesis has been addressed because of studies on the contribution of the Epstein-Barr virus (EBV) to the aggressiveness of nasopharyngeal carcinoma (NPC). Several EBV products modulate cancer progression phenomena, such as the epithelial-mesenchymal transition, cell motility, invasiveness, angiogenesis, and metastasis. In this regard, there are compelling data about the effects of EBV latent membrane proteins (LMPs) and EBV nuclear antigens (EBNAs), as well as nontranslated viral RNAs, such as the EBV-encoded small nonpolyadenylated RNAs (EBERs) and viral microRNAs, notably EBV miR-BARTs. The available data on the mechanisms and players involved in the contribution of EBV infection to the aggressiveness of NPC are discussed in this review. Overall, this conceptual framework may be valuable for the understanding of the contribution of some infectious agents in the progression of cancers.
authors.affiliation: Viral Carcinogenesis and Cancer Biology Research Group (ViriCan) at Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Brazil; Pathology Department at Botucatu Medical School, São Paulo State University (UNESP), Brazil. Electronic address: elgui@virican.net.
authors.forename: Deilson
authors.initials: D
authors.lastname: Elgui de Oliveira
authors.affiliation: Viral Carcinogenesis and Cancer Biology Research Group (ViriCan) at Biotechnology Institute (IBTEC), São Paulo State University (UNESP), Brazil.
authors.forename: Bárbara G
authors.initials: BG
authors.lastname: Müller-Coan
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Pagano
mesh_terms: D043925:Angiogenesis Inducing Agents; D063646:Carcinogenesis; D002277:Carcinoma / Q000150:complications / Q000821:virology; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D035683:MicroRNAs; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000150:complications / Q000821:virology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms; D012367:RNA, Viral; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D035683:MicroRNAs; D012367:RNA, Viral; D014763:Viral Matrix Proteins
keywords: Epstein–Barr virus; cancer progression; malignant invasion; metastasis; nasopharyngeal carcinoma