The Pasteurella multocida Toxin: A New Paradigm for the Link Between Bacterial Infection and Cancer

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.