Role of cMET in the development and progression of colorectal cancer

Juan Carlos Samamé Pérez-Vargas, Pamela Biondani, Claudia Maggi, Manuela Gariboldi, Annunziata Gloghini, Alessandro Inno, Chiara Costanza Volpi, Ambra Vittoria Gualeni, Maria di Bartolomeo, Filippo de Braud, Alessandra Castano, Ilaria Bossi, Filippo Pietrantonio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)18056-18077
Number of pages22
JournalInternational Journal of Molecular Sciences
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 3 2013

Keywords

  • Colorectal cancer
  • Hepatocyte growth factor
  • Mesenchymal-epithelial transition factor
  • Pathogenesis
  • Prognosis

ASJC Scopus subject areas

  • Computer Science Applications
  • Molecular Biology
  • Catalysis
  • Inorganic Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Physical and Theoretical Chemistry

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  • Cite this

    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. (2013). Role of cMET in the development and progression of colorectal cancer. International Journal of Molecular Sciences, 14(9), 18056-18077. https://doi.org/10.3390/ijms140918056