Role of p38 MAP Kinase Signal Transduction in Solid Tumors

Mitogen-activated protein kinases (MAPKs) mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the main subgroups, the p38 MAP kinases, has been implicated in a wide range of complex biologic processes, such as cell proliferation, cell differentiation, cell death, cell migration, and invasion. Dysregulation of p38 MAPK levels in patients are associated with advanced stages and short survival in cancer patients (e.g., prostate, breast, bladder, liver, and lung cancer). p38 MAPK plays a dual role as a regulator of cell death, and it can either mediate cell survival or cell death depending not only on the type of stimulus but also in a cell type specific manner. In addition to modulating cell survival, an essential role of p38 MAPK in modulation of cell migration and invasion offers a distinct opportunity to target this pathway with respect to tumor metastasis. The specific function of p38 MAPK appears to depend not only on the cell type but also on the stimuli and/or the isoform that is activated. p38 MAPK signaling pathway is activated in response to diverse stimuli and mediates its function by components downstream of p38. Extrapolation of the knowledge gained from laboratory findings is essential to address the clinical significance of p38 MAPK signaling pathways. The goal of this review is to provide an overview on recent progress made in defining the functions of p38 MAPK pathways with respect to solid tumor biology and generate testable hypothesis with respect to the role of p38 MAPK as an attractive target for intervention of solid tumors.