abstract
- Chronic inflammation is a risk factor for colorectal cancer. The MAPK-activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38-dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis-associated colon cancer (CAC) using the AOM/DSS model. Herein, we demonstrate that MK2(-/-) mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type C57BL/6 develop multiple neoplasms with the same treatment. MK2-specific cytokines IL-1, IL-6 and TNF-α were substantially decreased in AOM/DSS treated MK2(-/-) mouse colon tissues compared to wild type mice which coincided with a marked decrease in macrophage influx. Restoring MK2-competent macrophages by injecting wild type (WT) bone marrow derived macrophages into MK2(-/-) mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, was not sufficient to induce neoplasm development. Our results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC. This article is protected by copyright. All rights reserved.© 2015 UICC.