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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2011-6-15
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pubmed:abstractText |
The tyrosine kinase c-Met promotes the formation and malignant progression of multiple cancers. It is well known that c-Met hyperactivation increases tumorigenicity and tumor cell resistance to DNA damaging agents, properties associated with tumor-initiating stem cells. However, a link between c-Met signaling and the formation and/or maintenance of neoplastic stem cells has not been previously identified. Here, we show that c-Met is activated and functional in glioblastoma (GBM) neurospheres enriched for glioblastoma tumor-initiating stem cells and that c-Met expression/function correlates with stem cell marker expression and the neoplastic stem cell phenotype in glioblastoma neurospheres and clinical glioblastoma specimens. c-Met activation was found to induce the expression of reprogramming transcription factors (RFs) known to support embryonic stem cells and induce differentiated cells to form pluripotent stem (iPS) cells, and c-Met activation counteracted the effects of forced differentiation in glioblastoma neurospheres. Expression of the reprogramming transcription factor Nanog by glioblastoma cells is shown to mediate the ability of c-Met to induce the stem cell characteristics of neurosphere formation and neurosphere cell self-renewal. These findings show that c-Met enhances the population of glioblastoma stem cells (GBM SCs) via a mechanism requiring Nanog and potentially other c-Met-responsive reprogramming transcription factors.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/((3Z)-N-(3-chlorophenyl)-3-((3,5-dim...,
http://linkedlifedata.com/resource/pubmed/chemical/AC133 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/MYC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NANOG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/POU5F1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/SOX2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/SOXB1 Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:AngelaLiL,
pubmed-author:EberhartCharles GCG,
pubmed-author:GlasMartinM,
pubmed-author:Guerrero-CázaresHugoH,
pubmed-author:LalBachchuB,
pubmed-author:LaterraJohnJ,
pubmed-author:LiYunqingY,
pubmed-author:Quiñones-HinojosaAlfredoA,
pubmed-author:SangYingyingY,
pubmed-author:SchefflerBjornB,
pubmed-author:TrageserDanielD,
pubmed-author:XiaShuliS,
pubmed-author:YingMingyaoM
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pubmed:issnType |
Electronic
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pubmed:day |
14
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9951-6
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pubmed:meshHeading |
pubmed-meshheading:21628563-Animals,
pubmed-meshheading:21628563-Antigens, CD,
pubmed-meshheading:21628563-Flow Cytometry,
pubmed-meshheading:21628563-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21628563-Glioblastoma,
pubmed-meshheading:21628563-Glycoproteins,
pubmed-meshheading:21628563-Homeodomain Proteins,
pubmed-meshheading:21628563-Humans,
pubmed-meshheading:21628563-Immunoblotting,
pubmed-meshheading:21628563-Indoles,
pubmed-meshheading:21628563-Mice,
pubmed-meshheading:21628563-Mice, SCID,
pubmed-meshheading:21628563-Neoplasms, Experimental,
pubmed-meshheading:21628563-Neoplastic Stem Cells,
pubmed-meshheading:21628563-Nuclear Reprogramming,
pubmed-meshheading:21628563-Octamer Transcription Factor-3,
pubmed-meshheading:21628563-Peptides,
pubmed-meshheading:21628563-Phenotype,
pubmed-meshheading:21628563-Piperazines,
pubmed-meshheading:21628563-Proto-Oncogene Proteins c-met,
pubmed-meshheading:21628563-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:21628563-RNA Interference,
pubmed-meshheading:21628563-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:21628563-SOXB1 Transcription Factors,
pubmed-meshheading:21628563-Signal Transduction,
pubmed-meshheading:21628563-Sulfonamides,
pubmed-meshheading:21628563-Transplantation, Heterologous,
pubmed-meshheading:21628563-Tumor Cells, Cultured
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pubmed:year |
2011
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pubmed:articleTitle |
c-Met signaling induces a reprogramming network and supports the glioblastoma stem-like phenotype.
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pubmed:affiliation |
Hugo W Moser Research Institute at Kennedy Krieger, Baltimore, MD 21205, USA. LiYu@kennedykrieger.org
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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