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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-1-5
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pubmed:abstractText |
Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in primary samples and cell lines derived from GBM. TRPC6 is required for the development of the aggressive phenotype because knockdown of TRPC6 expression inhibits glioma growth, invasion, and angiogenesis. Functionally, TRPC6 causes a sustained elevation of intracellular calcium that is coupled to the activation of the calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Pharmacologic inhibition of the calcineurin-NFAT pathway substantially reduces the development of the malignant GBM phenotypes under hypoxia. Clinically, expression of TRPC6 was elevated in GBM specimens in comparison with normal tissues. Collectively, our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro and in vivo and that TRPC6 may be a promising therapeutic target in the treatment of human GBM.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1538-7445
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pubmed:author |
pubmed-author:BarreraDanielD,
pubmed-author:BushnevSergeyS,
pubmed-author:ChanSic LSL,
pubmed-author:ChigurupatiSrinivasuluS,
pubmed-author:KyriazisGeorge AGA,
pubmed-author:LathiaJustin DJD,
pubmed-author:MadanMeenuM,
pubmed-author:NaganathanAnushaA,
pubmed-author:PattisapuJogi VJV,
pubmed-author:PaulLeenaL,
pubmed-author:RichJeremy NJN,
pubmed-author:SugayaKiminobuK,
pubmed-author:VenkataramanRajarajeswariR
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
70
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
418-27
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pubmed:meshHeading |
pubmed-meshheading:20028870-Adult,
pubmed-meshheading:20028870-Blotting, Western,
pubmed-meshheading:20028870-Brain Neoplasms,
pubmed-meshheading:20028870-Cell Hypoxia,
pubmed-meshheading:20028870-Fluorescent Antibody Technique,
pubmed-meshheading:20028870-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:20028870-Glioblastoma,
pubmed-meshheading:20028870-Humans,
pubmed-meshheading:20028870-Immunohistochemistry,
pubmed-meshheading:20028870-NFATC Transcription Factors,
pubmed-meshheading:20028870-Neoplasm Invasiveness,
pubmed-meshheading:20028870-RNA, Small Interfering,
pubmed-meshheading:20028870-Receptor, Notch1,
pubmed-meshheading:20028870-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20028870-Signal Transduction,
pubmed-meshheading:20028870-TRPC Cation Channels
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pubmed:year |
2010
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pubmed:articleTitle |
Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness.
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pubmed:affiliation |
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Florida Hospital Cancer Institute, Orlando, Florida 32816, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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