The Cytotoxic Necrotizing Factor 1 from E. Coli: A Janus Toxin Playing with Cancer Regulators

Abstract

Certain strains of Escherichia coli have been indicated as a risk factor for colon cancer. E. coli is a normal inhabitant of the human intestine that becomes pathogenic, especially in extraintestinal sites, following the acquisition of virulence factors, including the protein toxin CNF1. This Rho GTPases-activating toxin induces dysfunctions in transformed epithelial cells, such as apoptosis counteraction, pro-inflammatory cytokines’ release, COX2 expression, NF-kB activation and boosted cellular motility. As cancer may arise when the same regulatory pathways are affected, it is conceivable to hypothesize that CNF1-producing E. coli infections can contribute to cancer development. This review focuses on those aspects of CNF1 related to transformation, with the aim of contributing to the identification of a new possible carcinogenic agent from the microbial world.

Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

“…Furthermore, the present study supports accumulating evidence that bacterial toxins may promote cancer [65][66][67][68][69][70] and conceptually demonstrates how bacterial toxins may contribute to cancer by influencing the crosstalk between tumor and immune cells. For personal use only.…”

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 induces epithelial mesenchymal transition

“…Of note, previous studies disclosing that CNF1-treated cells are reminiscent of transformed cells (Fabbri, Travaglione, Ballan, Loizzo, & Fiorentini, 2013) had been principally conducted in already transformed cells. In contrast, when CNF1 was administrated to nontransformed IEC-6 cells, neither signs of EMT nor activation of pathways leading to EMT were observed.…”

Inflammation and colorectal cancer, when microbiota-host mutualism breaks

“…Also, CNF1 induces quiescent cells to enter the cell cycle and undergo DNA synthesis [124] , interferes with normal cytokinesis, resulting in the production of multinucleated cells and in the onset of aneuploidia. As cancer may arise when the same regulatory pathways are affected, it is conceivable that CNF1-producing E. coli infections can contribute to cancer development [125] . Our hypothesis is that these bacteria may act as passengers, reinforcing and favoring but not causing the development of colorectal cancer.…”