Xenophagy in Helicobacter pylori- and Epstein-Barr virus-induced gastric cancer

J Pathol. 2014 Jun;233(2):103-12. doi: 10.1002/path.4351.

Abstract

Helicobacter pylori and Epstein-Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double-membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori- and EBV-induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal-lysosomal pathway for degradation. In this connection, H. pylori or EBV-induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori- and EBV-induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents.

Keywords: EBV; H. pylori; autophagy; gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Cell Transformation, Neoplastic / pathology*
  • Cell Transformation, Viral
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / virology*
  • Helicobacter Infections / complications
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / metabolism
  • Helicobacter pylori / pathogenicity*
  • Herpesvirus 4, Human / growth & development
  • Herpesvirus 4, Human / metabolism
  • Herpesvirus 4, Human / pathogenicity*
  • Humans
  • Stomach Neoplasms / microbiology
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / virology
  • Virulence Factors / metabolism
  • Virus Replication

Substances

  • Virulence Factors