Blockade of MK2 is protective in inflammation-associated colorectal cancer development

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). Herein, we demonstrate that MK2^-/- mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type (WT) 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 with WT mice, which coincided with a marked decrease in macrophage influx. Restoring MK2-competent macrophages by injecting WT bone marrow derived macrophages into MK2^-/- mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, macrophages were not sufficient to induce neoplasm development. These results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC. What's new? The role of inflammation in cancer development is intriguing, especially in colitis-associated colon cancer. Here the authors examine the role of MAP kinase-activated protein kinase 2 (MK2) in this process. They show that MK2^-/- mice produce less cytokines (IL-1, IL-6 and TNF-alpha) and are highly resistant to cancer development, a process only partially reversed by transfusion of wildtype macrophages. The data identify MK2 as an inflammatory regulator in colon cancer development and a possible new drug target for this disease.