Mitogen-Activated Protein Kinase Signal Transduction in Solid Tumors

Abstract

Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in responseto extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ERK2), c-Jun N(JNK/SAPK), p38 MAPK(p38α, p38β, p38γ and p38δ), and ERK3/ ERK4/ ERK5. Whenstimulated, factors of upstream or downstream change, and by interacting with each other, these groups havelong been recognized to be related to multiple biologic processes such as cell proliferation, differentiation,death, migration, invasion and inflammation. However, once abnormally activated, cancer may occur. Severalcomponents of the MAPK network have already been proposed as targets in cancer therapy, such as p38, JNK,ERK, MEK, RAF, RAS, and DUSP1. Among them, alteration of the RAS-RAF-MEK-ERK-MAPK(RAS-MAPK)pathway has frequently been reported in human cancer as a result of abnormal activation of receptor tyrosinekinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell deathare controversial, so that further in-depth investigations are needed to address these controversies. Based onan extensive analysis of published data, the goal of this review is to provide an overview on recent studies aboutthe mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.