Role of Helicobacter pylori virulence factor cytotoxin-associated gene A in gastric mucosa-associated lymphoid tissue lymphoma

World J Gastroenterol. 2013 Dec 7;19(45):8219-26. doi: 10.3748/wjg.v19.i45.8219.

Abstract

Helicobacter pylori (H. pylori) infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue (MALT). Increasing evidence shows that eradication of H. pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission. The eradication of H. pylori is the standard care for patients with gastric MALT lymphoma. Cytotoxin-associated gene A (CagA) protein, one of the most extensively studied H. pylori virulence factors, is strongly associated with the gastric MALT lymphoma. CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races. After being translocated into B lymphocytes via type IV secretion system, CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and -independent manners and/or some other pathways, and thereby promotes lymphomagenesis. A variety of proteins including p53 and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA. Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.

Keywords: Cytotoxin-associated gene A; Gastric mucosa-associated lymphoid tissue lymphoma; Helicobacter pylori; Lymphomagenesis; Molecular mechanism.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Cell Transformation, Neoplastic / metabolism
  • Gastric Mucosa / microbiology*
  • Genotype
  • Helicobacter Infections / complications
  • Helicobacter Infections / genetics
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / metabolism*
  • Helicobacter pylori / pathogenicity
  • Humans
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / metabolism
  • Lymphoma, B-Cell, Marginal Zone / microbiology*
  • Phenotype
  • Prognosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / microbiology*
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Virulence Factors
  • cagA protein, Helicobacter pylori