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Abstract
The role of mitogen-activated protein kinases (MAPKs) in regulation of inflammation is well known. MAPK family is activated by various stimuli and involved in transmitting extracellular signals to nucleus leading to gene regulation. Inflammation is primary defensive response of host against microbes. Controlled inflammation is helpful and indispensable for host defense. However, uncontrolled inflammatory response leads to various inflammatory diseases and cancer. Persistent inflammation leads to cell proliferation and survival that plays crucial role in tumorigenesis. In this review, we recapitulate the recent knowledge of MAPK signaling and its roles in inflammation-associated carcinogenesis.
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Figure 1.
MAPK signaling pathways and cancer development. The MAPK signaling pathways are stimulated by pathogen-associated molecular patterns (PAMPs), growth factors (GF), tumor necrosis factor (TNF), stress, and inflammatory cytokines. Stimulation of MEK1/2 results in activation of MAPK (ERK1/2) activity. Activation of MEK4/7 is responsible for the activation of JNKs. The phosphorylation of p38 is regulated by MKK3/6. ERK1/2, JNK, and p38 activate various transcription factors such as TCF/ELK1, AP-1, ATF-2, and others. Different transcription factors including these result in expression of genes encoding pro-inflammatory cytokines, cell proliferation related proteins, growth factors, and anti-apoptotic factors. These factors are related with cancer development.
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