Mitogen-activated protein kinase signal transduction in solid tumors.
Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to 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. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long 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. Several components 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 tyrosine kinases or gain-of-function mutations in genes. The reported roles of MAPK signaling in apoptotic cell death are controversial, so that further in-depth investigations are needed to address these controversies. Based on an extensive analysis of published data, the goal of this review is to provide an overview on recent studies about the mechanism of MAP kinases, and how it generates certain tumors, as well as related treatments.
Department of Pathology, the First Affiliated Hospital of Nanchang University E-mail : mjhdoctor@126.com, wclac0249@126.com.
Yuan-Yuan
YY
Lei
Wei-Jia
WJ
Wang
Jin-Hong
JH
Mei
Chun-Liang
CL
Wang
D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002681:China / Q000453:epidemiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases