Ontology type: schema:ScholarlyArticle Open Access: True
2015-08
AUTHORSKate Lynn J Bill, Jeannine Garnett, Xiaoyan Ma, Caitlin D May, Svetlana Bolshakov, Alexander J Lazar, Dina C Lev, Raphael E Pollock
ABSTRACTDedifferentiated liposarcomas (DDLPS) are highly resistant to conventional chemo- and radiotherapies, with surgical resection remaining the classic treatment strategy; therefore, there is a pressing need for novel anti-DDLPS-targeted chemotherapeutics. Hepatocyte growth factor receptor (Met) expression is elevated in DDLPS, but the functional role of Met signaling in this disease is not known. We found that the in vitro stimulation of DDLPS cells with hepatocyte growth factor (HGF) elevated the degree of PI3K/AKT and MAPK pathway signaling, and that pro-tumorigenic phenotypes such as cell proliferation, invasion, and migration were significantly enhanced. Conversely, Met knockdown using shRNA-mediated interference decreased HGF-induced Met signaling, the invasive and migratory nature of DDLPS cells in vitro, and the tumorigenicity of DDLPS cells in vivo. These data strongly support the role for Met as a DDLPS therapeutic target. To that end, using EMD1214063, an ATP-competitive kinase inhibitor that targets Met more specifically than other kinases, inhibited Met-dependent signaling, reduced the oncogenicity of DDLPS cells in vitro, and significantly increased the survival of nude mice bearing subcutaneous DDLPS xenografts. These findings support further investigations of HGF-induced Met signaling inhibition in DDLPS, as a potential strategy to enhance clinical outcomes for this disease. More... »
PAGES951-961
http://scigraph.springernature.com/pub.10.1038/labinvest.2015.62
DOIhttp://dx.doi.org/10.1038/labinvest.2015.62
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PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/26006023
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]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/labinvest.2015.62'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/labinvest.2015.62'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/labinvest.2015.62'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/labinvest.2015.62'
This table displays all metadata directly associated to this object as RDF triples.
333 TRIPLES
21 PREDICATES
90 URIs
35 LITERALS
23 BLANK NODES