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Role of cMET in the Development and Progression of Colorectal Cancer
Medical Oncology Department, Arnau de Vilanova Universitary Hospital, 25198 Lleida, Spain
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1-20133 Milan, Italy
Experimental Oncology and Molecular Medicine Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1-20133 Milan, Italy
FIRC Institute of Molecolar Oncology Foundation (IFOM), 1-20133 Milan, Italy
Pathology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian, 1-20133 Milan, Italy
Medical Oncology, Sacro Cuore-Don Calabria Hospital, 37024 Negrar (Verona), Italy
* Author to whom correspondence should be addressed.
Received: 25 July 2013; in revised form: 13 August 2013 / Accepted: 27 August 2013 / Published: 3 September 2013
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.