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http://purl.uniprot.org/citations/18628476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18628476http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

The Met receptor tyrosine kinase and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), are involved in a wide range of biological activities, including cell proliferation, motility, invasion, and angiogenesis. The HGF/SF-Met signaling pathway is frequently activated in a variety of cancers, and uncontrolled Met activation correlates with highly invasive tumors and poor prognosis. In this study, we investigated the inhibitory effect of a novel soluble splice variant of Met on the HGF/SF-Met pathway.

Experimental design

Using our alternative splicing modeling platform LEADS, we have identified a novel splice variant of the Met receptor, which encodes a truncated soluble form of the receptor. This variant was produced as a recombinant Fc-fused protein named Cgen-241A and was tested in various cell-based assays representing different outcomes of the HGF/SF-Met pathway.

Results

Cgen-241A significantly inhibited HGF/SF-induced Met phosphorylation as well as cell proliferation and survival. In addition, Cgen-241A showed a profound inhibitory effect on cell scattering, invasion, and urokinase up-regulation. The inhibitory effects of Cgen-241A were shown in multiple human and nonhuman cell types, representing different modes of Met activation. Furthermore, Cgen-241A showed direct binding to HGF/SF.

Conclusions

Taken together, our results indicate that Cgen-241A is a potent antagonist of the HGF/SF-Met pathway, underlining its potential as a therapeutic agent for the treatment of a wide variety of human malignancies that are dependent on this pathway."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-08-0108"xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Chen A."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Oren A."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Rotman G."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Beiman M."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Dassa L."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Levine Z."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Tiran Z."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Koifman C."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Tsarfaty I."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Horev J."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Amitai H."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Ayalon-Soffer M."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Bahat K."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Glezer S."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Handelsman T."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Hermesh C."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Israel C."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Peres Y."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Pergam T."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Vidal-Finkelstein R."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/author"Landesman-Milo D."xsd:string
http://purl.uniprot.org/citations/18628476http://purl.uniprot.org/core/date"2008"xsd:gYear
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