Article

MET signalling: principles and functions in development, organ regeneration and cancer.

Institute for Cancer Research and Treatment (IRCC), University of Torino Medical School, 10060 Candiolo, Torino, Italy.
Nature Reviews Molecular Cell Biology (Impact Factor: 37.16). 12/2010; 11(12):834-48. DOI: 10.1038/nrm3012
Source: PubMed

ABSTRACT The MET tyrosine kinase receptor (also known as the HGF receptor) promotes tissue remodelling, which underlies developmental morphogenesis, wound repair, organ homeostasis and cancer metastasis, by integrating growth, survival and migration cues in response to environmental stimuli or cell-autonomous perturbations. The versatility of MET-mediated biological responses is sustained by qualitative and quantitative signal modulation. Qualitative mechanisms include the engagement of dedicated signal transducers and the subcellular compartmentalization of MET signalling pathways, whereas quantitative regulation involves MET partnering with adaptor amplifiers or being degraded through the shedding of its extracellular domain or through intracellular ubiquitylation. Controlled activation of MET signalling can be exploited in regenerative medicine, whereas MET inhibition might slow down tumour progression.

0 Bookmarks
 · 
99 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpression of the HGF, have been reported in a substantial subgroup of NSCLC patients resistant to EGFR-TKIs. Several cMET-inhibitors have been developed as potential therapeutic candidates, and are currently under investigation in clinical trials. These compounds include both monoclonal antibodies and TKIs, and most of them have been investigated as dual combinations including an anti-EGFR TKI, to improve the efficacy of the available treatments, and ultimately overcome acquired resistance to EGFR-inhibitors.
    Current Drug Targets 12/2014; 15(14):1284-92. · 3.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Met is a tyrosine kinase receptor that is considered to be a proto-oncogene. The hepatocyte growth factor (HGF)-Met signaling system plays an important role in tumor growth, invasion, and metastasis in many types of malignancies. Furthermore, Met expression has been reported to be a useful predictive biomarker for disease progression and patient survival in these malignancies. Many studies have focused on the clinical significance and prognostic role of Met in urological cancers, including prostate cancer (PCa), renal cell carcinoma (RCC), and urothelial cancer. Several preclinical studies and clinical trials are in progress. In this review, the current understanding of the pathological role of Met in cancer cell lines, its clinical significance in cancer tissues, and its predictive value in patients with urological cancers are summarized. In particular, Met-related malignant behavior in castration-resistant PCa and the different pathological roles Met plays in papillary RCC and other histological types of RCC are the subjects of focus. In addition, the pathological significance of phosphorylated Met in these cancers is shown. In recent years, Met has been recognized as a potential therapeutic target in various types of cancer; therapeutic strategies used by Met-targeted agents in urological cancers are summarized in this review.
    Cancers. 12/2014; 6(4):2387-403.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effective treatment for cerebral ischemia has not yet been established. Hepatocyte growth factor (HGF) is a potent pleiotropic cytokine that is involved in cell and tissue regeneration, including in the central nervous system. Studies have demonstrated that an exogenous administration of HGF protects brain tissue from ischemic damage. In response to binding to the receptor c-Met, HGF activates the downstream signaling pathways (including the phosphatidylinositol 3-kinase/Akt, Ras/MAPK and signal transducer and activator of transcription pathways) which leads to various cellular responses involved in angiogenesis, glial scar formation, anti-apoptosis and neurogenesis. The purpose of this review is to summarize the present understanding of the therapeutic potential of HGF in cerebral ischemia.
    Experimental and therapeutic medicine 02/2015; 9(2):283-288. · 0.94 Impact Factor

Full-text (2 Sources)

Download
20 Downloads
Available from
May 22, 2014

Similar Publications