Regulation of the MET oncogene: molecular mechanisms.

摘要: The MET oncogene is a predictive biomarker and an attractive therapeutic target for various cancers. Its expression regulated at multiple layers via mechanisms. It subject to epigenetic modifications, i.e. DNA methylation histone acetylation. Hypomethylation acetylation of the gene have been associated with its high in some Multiple transcription factors including Sp1 Ets-1 govern transcription. After transcription, METmRNA spliced into species nucleus before being transported cytoplasm where translation modulated by least 30 microRNAs initiation factors, e.g. eIF4E eIF4B. produces single chain pro-Met protein 170 kDa which cleaved α β chains. These two chains are bound together through disulfide bonds form heterodimer undergoes either N-linked or O-linked glycosylation Golgi apparatus it properly localized membrane. Upon interactions ligand, hepatocyte growth factor (HGF), activity Met kinase boosted phosphorylation mechanisms signal relayed downstream pathways. phosphorylated then internalized subsequent degradation recycle proteasome, lysosome endosome Moreover, autoregulation activation other EGFRs G-protein coupled receptors. Since deregulation leads cancer pathological conditions, better understanding regulation critical Met-targeted therapeutics.