Abstract
Infections are estimated to contribute to 20% of all human tumours. These are mainly caused by viruses, which explains why a direct bacterial contribution to cancer formation has been largely ignored. While epidemiological data link bacterial infections to particular cancers, tumour formation is generally assumed to be solely caused by the ensuing inflammation responses. Yet, many bacteria directly manipulate their host cell in various phases of their infection cycle. Such manipulations can affect host cell integrity and can contribute to cancer formation. We here describe how bacterial surface moieties, bacterial protein toxins and bacterial effector proteins can induce host cell DNA damage, and thereby can interfere with essential host cell signalling pathways involved in cell proliferation, apoptosis, differentiation and immune signalling.
Highlights
Cancer development is the result of a series of genetic modifications that alter the normal control of cell growth and survival
Bacterially induced host cell manipulation can promote cancer formation, it is unlikely that bacterial pathogens themselves experience any evolutionary benefit from their carcinogenic actions
Box 1: In need of answers (i) Do bacterial infections only decrease the threshold for cellular transformation or can they initiate tumour formation?
Summary
Cancer development is the result of a series of genetic modifications that alter the normal control of cell growth and survival. An even more compelling case for the link between viral infections and cancer arose from experiments showing that viruses exploit the host cell niche for their infection cycle and as a result stimulate mammalian growth-inducing genes, leaving the cells in a cancerous state of uncontrolled cell division It is understood how viruses such as hepatitis B virus and human papillomavirus types 5 and 8 cause cellular transformation by inducing genetic instability through viral integration and through the activation of a large number of signalling pathways and cellular genes involved in oncogenesis, proliferation, inflammation and immune responses [9,10]. Studies with germ-free and wild-type mice showed that TLR4 activation by LPS from the intestinal microbiota pool contributes to the promotion of injury- and inflammationdriven hepatocellular carcinoma by activating proliferative and antiapoptotic signals [19] Findings from these animal studies were further corroborated by human studies in which enhanced expression of the TLR4/MyD88 complex was detected in 20% of colorectal patient samples [45].
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