The Four Horsemen in Colon Cancer

Figure 2

Oncogenic activity of Bacteroides fragilis and Salmonella enterica. (a) Enterotoxigenic Bacteroides fragilis (ETBF) stimulates carcinogenesis in colonic epithelium through the BFT toxin. This toxin leads to an increase in reactive oxygen species (ROS) by inducing spermine oxidase expression via c-Myc. Likewise, BFT cuts E-cadherin, thus activating β catenin which stimulates cellular proliferation. BFT also modulates the host’s immune response by promoting Treg lymphocytes to polarize the response to Th17 lymphocytes, thus increasing IL-17 secretion which in turn, activates NF-κB in the colonic epithelium; this results in the secretion of the chemokines CXCL1, CXCL2 and CXCL5 that recruit MDSC, thus favoring evasion from the immune response. The presence of ETBF has also been associated with STAT3 activation. (b). Salmonella enterica releases two proteins that promote carcinogenesis: the typhoid toxin that induces cellular proliferation, and the AvrA protein that is internalized via the Type 3 Secretion System(T3SS). AvrA activates the β catenin and STAT3 pathways, and also causes the acetylation of p53. Additionally, Salmonella enterica leads to the activation of the MAPK/AKT pathway. The activation of these pathways promotes an increase in proliferation and cellular differentiation, and decreases apoptosis.

(a)

(b)