CagA

Helicobacter pylori virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb cag pathogenicity island (PAI).[1] H. pylori strains can be divided into CagA positive or negative strains. Around 60% of H. pylori isolates in Western countries are positive, whereas the majority of East Asian isolates are positive.[1]

The cag PAI also encodes for a type 4 secretion system which is used to "inject" CagA into a target cell upon H. pylori attachment. After translocation, CagA localises to the inner surface of the cell membrane and undergoes tyrosine phosphorylation by Src family kinases (e.g. Fyn and Lyn).[1]

Role in Cancer

H. pylori infection is associated with MALT lymphoma and gastric adenocarcinoma and CagA is thought to be involved in cancer development.[2] Phosphorylated CagA is able to interact with the SHP-2 tyrosine phosphatase, rendering it functionally active, triggering a host cell morphological change to a more motile phenotype known as the "hummingbird phenotype".[1] This phenotype mimics an effect produced by hepatocyte growth factor which may participate in various aspects of cancer, including metastasis.[2] CagA is also a highly antigenic protein that is associated with a prominent inflammatory response by eliciting interleukin-8 production.[3]

References

  1. 1 2 3 4 Hatakeyama, M.; Higashi, H. (2005). "Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis". Cancer Science. 96: 835–843. doi:10.1111/j.1349-7006.2005.00130.x. PMID 16367902.
  2. 1 2 Lax, A. (2005). "Bacterial toxins and cancer — a case to answer?". Nature Reviews Microbiology. 3: 343–9. doi:10.1038/nrmicro1130. PMID 15806096.
  3. ↑ Yamaoka Y (November 2010). "Mechanisms of disease: Helicobacter pylori virulence factors". Nat Rev Gastroenterol Hepatol. 7 (11): 629–41. doi:10.1038/nrgastro.2010.154. PMC 3137895Freely accessible. PMID 20938460.

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