Cancer cells rely on invasive growth to survive in a hostile microenvironment; this growth is characterised by interconnected processes such as epithelial-to-mesenchymal transition and migration. A master regulator of these events is the MET oncogene, which is overexpressed in the majority of cancers; however, since mutations in the MET oncogene are seen only rarely in cancers and are relatively infrequent, the mechanisms that cause this widespread MET overexpression remain obscure. Here, we show that the 5' untranslated region (5'UTR) of MET mRNA harbours two functional stress-responsive elements, conferring translational regulation by the integrated stress response (ISR), regulated by phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) at serine 52.
View Article and Find Full Text PDFTargeted therapy significantly impairs tumour growth but suffers from limitations, among which the 'flare' ('rebound') effect. Among cancers driven by tyrosine kinase receptors, those relying on alterations of the MET oncogene benefit from treatment by specific inhibitors. Previously, we reported that discontinuation of MET tyrosine kinase receptor inhibition causes 'rebound' activation of the oncogene, with a post-treatment transient hyperphosphorylation phase that culminates into a dramatic increase in cancer cell proliferation.
View Article and Find Full Text PDFis an oncogene encoding the tyrosine kinase receptor for hepatocyte growth factor (HGF). Upon ligand binding, MET activates multiple signal transducers, including PI3K/AKT, STAT3, and MAPK. When mutated or amplified, becomes a "driver" for the onset and progression of cancer.
View Article and Find Full Text PDFThis series consists of 25 patients affected with nasopharyngeal carcinoma in an advanced stage (T3-T4) treated at the Radiation Oncology department of the Institute of Radiology, University "La Sapienza", Rome, from 1978 through 1988. The patients were irradiated with X-rays produced by a LinAc with 4 MeV energy, for a total dose of 60/75 Gy on tumor and 50/60 Gy on nodes. In 7 cases radiation therapy was combined with chemotherapy.
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