Abstract: Mesenchymal-epithelial transition (MET) is a member of a distinct subfamily of heterodimeric receptor tyrosine kinase receptors that specifically binds the hepatocyte growth factor (HGF). Binding to HGF leads to receptor dimerization/multimerization and phosphorylation, resulting in its catalytic activation. MET activation drives the malignant progression of several tumor types, including colorectal cancer (CRC), by promoting signaling cascades that mainly result in alterations of cell motility, survival, and proliferation. MET is aberrantly activated in many human cancers through various mechanisms, including point mutations, gene amplification, transcriptional up-regulation, or ligand autocrine loops. MET promotes cell scattering, invasion, and protection from apoptosis, thereby acting as an adjuvant pro-metastatic gene for many tumor types. In CRC, MET expression confers more aggressiveness and worse clinical prognosis. With all of this rationale, inhibitors that target the HGF/MET axis with different types of response have been developed. HGF and MET are new promising targets to understand the pathogenesis of CRC and for the development of new, targeted therapies.
Keywords: colorectal cancer; hepatocyte growth factor; mesenchymal-epithelial transition factor; pathogenesis; prognosis
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Pérez-Vargas, J.C.S.; Biondani, P.; Maggi, C.; Gariboldi, M.; Gloghini, A.; Inno, A.; Volpi, C.C.; Gualeni, A.V.; di Bartolomeo, M.; de Braud, F.; Castano, A.; Bossi, I.; Pietrantonio, F. Role of cMET in the Development and Progression of Colorectal Cancer. Int. J. Mol. Sci. 2013, 14, 18056-18077.
Pérez-Vargas JCS, Biondani P, Maggi C, Gariboldi M, Gloghini A, Inno A, Volpi CC, Gualeni AV, di Bartolomeo M, de Braud F, Castano A, Bossi I, Pietrantonio F. Role of cMET in the Development and Progression of Colorectal Cancer. International Journal of Molecular Sciences. 2013; 14(9):18056-18077.
Pérez-Vargas, Juan C.S.; Biondani, Pamela; Maggi, Claudia; Gariboldi, Manuela; Gloghini, Annunziata; Inno, Alessandro; Volpi, Chiara C.; Gualeni, Ambra V.; di Bartolomeo, Maria; de Braud, Filippo; Castano, Alessandra; Bossi, Ilaria; Pietrantonio, Filippo. 2013. "Role of cMET in the Development and Progression of Colorectal Cancer." Int. J. Mol. Sci. 14, no. 9: 18056-18077.