Article

MET signaling: 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: 36.46). 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.

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Available from: Livio Trusolino, Dec 30, 2013
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    • "As the clinical HDI course is pursued, it is becoming important to identify the potential mechanisms of resistance to increase efficacy and identify potential drug combinations. MET, a transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF), plays an important role in the development of both human cancer and drug resistance in cancer cells [10] [11] [12]. "
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    • "kB target gene ) ( Harrison and Farzaneh , 2000 ) . This was excluded , at least in epithelial cell lines , by lack of HGF mRNA or protein expres - sion after TNF - a treatment . ( ii ) Second , as it was shown that MET can be activated by physical interaction with other sur - face receptors , including molecules lacking tyrosine kinase activity ( Trusolino et al . , 2010 ) , we hypothesized that the acti - vated TNF receptor could oligomerize with MET . This was ruled out by lack of receptor co - precipitation , and by lack of receptor co - localization after fluorescent immunostaining and confocal microscopy . We can also hypothesize that MET phosphorylation is mediated by an intracellular kinase . A l"
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    • "After satellite cell activation, expression of muscle regulatory factors, Myf5 and MyoD occurs, and at the beginning of differentiation, myogenin and MRF4 are expressed [8]. When HGF binds to the c-Met receptor tyrosine kinase, its cytoplasmic Tyr residues are autophosphorylated and bind the scaffolding adaptor protein Gab1, which leads to the activation of phosphatidylinositol 3-kinase (PI3K) and Ras-ERK mitogen-activated protein kinase cascade (Fig. 1) [9]. This suggests that controlled activation of c-Met signaling can be exploited in regenerative medicine. "
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