ERK5 is a critical mediator of inflammation-driven cancer

Abstract

Chronic infl ammation is a hallmark of many cancers, yet the pathogenic mechanisms that distinguish cancer-associated in flammation from benign persistent in flammation are still mainly unclear. Here, we report that the protein kinase ERK5 controls the expression of a speci fic subset of inflammatory mediators in the mouse epidermis, which triggers the recruitment of infl ammatory cells needed to support skin carcinogenesis. Accordingly, inactivation of ERK5 in keratinocytes prevents infl ammation-driven tumorigenesis in this model. In addition, we found that anti-ERK5 therapy cooperates synergistically with existing antimitotic regimens, enabling efficacy of subtherapeutic doses. Collectively, our findings identified ERK5 as a mediator of cancer-associated in flammation in the setting of epidermal carcinogenesis. Considering that ERK5 is expressed in almost all tumor types, our findings suggest that targeting tumor-associated in fl ammation via anti-ERK5 therapy may have broad implications for the treatment of human tumors. Cancer Res; 75(4); 742 - 53. -2015 AACR. -