Viral Carcinogenesis Beyond Malignant Transformation: EBV in the Progression of Human Cancers

Trends Microbiol. 2016 Aug;24(8):649-664. doi: 10.1016/j.tim.2016.03.008. Epub 2016 Apr 7.

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.

Keywords: Epstein–Barr virus; cancer progression; malignant invasion; metastasis; nasopharyngeal carcinoma.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inducing Agents
  • Carcinogenesis*
  • Carcinoma / complications
  • Carcinoma / virology
  • Cell Movement
  • Cell Transformation, Neoplastic
  • Cell Transformation, Viral
  • Disease Progression*
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / virology
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / pathogenicity*
  • Herpesvirus 4, Human / physiology
  • Humans
  • MicroRNAs
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / complications
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms
  • RNA, Viral
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism

Substances

  • Angiogenesis Inducing Agents
  • MicroRNAs
  • RNA, Viral
  • Viral Matrix Proteins