| dc.description | Patients with inflammatory bowel disease (IBD) are at heightened risk for colorectal cancer (CRC). The molecules interleukin (IL)-1beta, nuclear factor (NF)-kappaB, and cyclooxygenase (COX)-2 have been implicated in both IBD and CRC. We have previously demonstrated that IL-1beta promotes survival of intestinal epithelial cells (IECs) during detachment induced cell death, or anoikis. In this study, we demonstrate that detachment results in activation of NF-kappaB which conveys a survival advantage to IECs during anoikis, and that IL-1beta enhances this effect. IL-1beta is appreciated to induce COX2, which is rate limiting in the production of prostaglandins (PG). PGs also promote survival during IEC anoikis as does the downstream signaling molecule cAMP. We also demonstrate that COX2 expression is regulated by NF-kappaB, and that in the presence of NF-kappaB blockade, cAMP is sufficient to restore IEC viability during anoikis. Taken together, these data suggest that IL-1beta induction of NF-kappaB/COX2/PG/cAMP signaling is one mechanism of promoting IEC viability during anoikis. Taken together this suggests that regulation of anoikis by IL-1beta or PG and associated signaling is a potential link between chronic inflammation and cancer in the intestine. | en_US |
