Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer

Abstract

The p38α mitogen-activated protein kinase pathway not only regulates the production of inflammatory mediators, but also controls processes related to tissue homeostasis, such as cell proliferation, differentiation and survival, which are often disrupted during malignant transformation. The versatility of this signaling pathway allows for the regulation of many specific functions depending on the cell type and context. Here, we discuss mouse models that have been used to identify in vivo functions of p38α signaling in the pathogenesis of inflammatory diseases and cancer. Experiments using genetically modified mice and pharmacological inhibitors support that targeting the p38α pathway could be therapeutically useful for some inflammatory diseases and tumor types.

Keywords: cancer; inflammation; mouse models; p38 MAPK; signaling pathways; therapy; tumor initiation; tumor promotion.

Figure 1

Implication of p38α MAPK in mouse models of inflammatory diseases. For details, see Table 1.

Figure 2

Regulation of tumorigenesis by p38α MAPK in mouse models of cancer. Key molecules and processes are indicated. For further details, see Table 1. Normal cells are indicated in beige and tumor cells are indicated in blue. Breast and lung tumor cells treated with cisplatin rely on p38α for survival. The link between PRAK and angiogenesis has been reported in endothelial cells.