Linking epithelial polarity and carcinogenesis by multitasking Helicobacter pylori virulence factor CagA

Oncogene. 2008 Nov 24;27(55):7047-54. doi: 10.1038/onc.2008.353.


Loss of cell polarity and tissue architecture is a hallmark of carcinomas that arise from epithelial cells. Recent studies on Drosophila tumor suppressors have provided evidence that epithelial polarity and cell proliferation are functionally coupled, suggesting a function for polarity defects in the development of carcinomas. This notion is supported by the findings that mammalian orthologs of these Drosophila tumor suppressors are targeted by a number of viral oncoproteins. Chronic infection with Helicobacter pylori is causally associated with gastric carcinoma. H. pylori virulence factor CagA (cytotoxin-associated gene A), which is delivered into gastric epithelial cells through a bacterial type IV secretion system, has an important function in cell transformation through interacting with and deregulating SHP-2 phosphatase, a bona fide oncoprotein that is associated with human malignancies. Recent studies have further revealed that CagA specifically binds and inhibits PAR1/MARK polarity-regulating kinase, thereby causing junctional and polarity defects in epithelial cells. Thus, the bacterial oncoprotein simultaneously targets the polarity-regulating system and growth-regulatory system. These findings indicate that loss of cell polarity underlies the abnormal proliferation of epithelial cells that directs carcinogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Bacterial / metabolism
  • Antigens, Bacterial / physiology*
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology*
  • Carcinoma / etiology
  • Carcinoma / metabolism
  • Cell Polarity / genetics
  • Cell Polarity / physiology*
  • Cell Transformation, Neoplastic / pathology*
  • Epithelial Cells / pathology*
  • Epithelial Cells / physiology*
  • Gastric Mucosa / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori / metabolism
  • Helicobacter pylori / pathogenicity
  • Helicobacter pylori / physiology*
  • Humans
  • Models, Biological
  • Protein Transport
  • Signal Transduction / physiology
  • Stomach / pathology
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / metabolism
  • Virulence Factors / physiology


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