Description

Inflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.

Publication Title

MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.

Sample Metadata Fields

Specimen part, Disease, Disease stage