The Pasteurella multocida toxin: a new paradigm for the link between bacterial infection and cancer

Curr Top Microbiol Immunol. 2012:361:131-44. doi: 10.1007/82_2012_236.

Abstract

The concept that bacterial infection could cause cancer has only recently become accepted because of the strong epidemiological and molecular evidence for a major carcinogenic role played by Helicobacter pylori. However, information on other potential bacterial carcinogens is very limited and thereby unconvincing. A different approach is to assess bacteria for potentially pro-carcinogenic properties. The Pasteurella multocida toxin (PMT) has many properties that mark it out as a potential carcinogen. PMT is a highly potent mitogen and has been demonstrated to block apoptosis. PMT modifies and activates members of three of the four families of heterotrimeric G-proteins, all of which have potential roles in carcinogenesis. Many signalling components downstream of these G-proteins are known proto-oncogenes and have been shown to be activated by PMT. These include, amongst others, the Rho GTPase, focal adhesion kinase, cyclooxygenase-2, β-catenin signalling and calcium signalling. PMT action potentially influences many of the acquired Hanahan/Weinberg capabilities necessary for oncogenic transformation. Although there is little evidence that PMT might have a role in human cancer, it serves as an important and novel paradigm for a bacterial link to cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Cell Transformation, Neoplastic
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Neoplasms / etiology
  • Neoplasms / metabolism
  • Neoplasms / microbiology
  • Pasteurella Infections / complications
  • Pasteurella Infections / metabolism
  • Pasteurella Infections / microbiology
  • Pasteurella multocida / genetics
  • Pasteurella multocida / metabolism*
  • Pasteurella multocida / pathogenicity
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Signal Transduction*
  • Up-Regulation
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Pasteurella multocida toxin
  • Protein Subunits
  • beta Catenin
  • Cyclooxygenase 2
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Heterotrimeric GTP-Binding Proteins