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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 |
2011-1-21
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pubmed:abstractText |
We show that in melanoma cells oncogenic BRAF, acting through MEK and the transcription factor BRN2, downregulates the cGMP-specific phosphodiesterase PDE5A. Although PDE5A downregulation causes a small decrease in proliferation, its major impact is to stimulate a dramatic increase in melanoma cell invasion. This is because PDE5A downregulation leads to an increase in cGMP, which induces an increase in cytosolic Ca(2+), stimulating increased contractility and inducing invasion. PDE5A downregulation also this leads to an increase in short-term and long-term colonization of the lungs by melanoma cells. We do not observe this pathway in NRAS mutant melanoma or BRAF mutant colorectal cells. Thus, we show that in melanoma cells oncogenic BRAF induces invasion through downregulation of PDE5A.
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pubmed:grant |
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pubmed:commentsCorrections |
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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/BRAF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cardiac Myosins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/Heterocyclic Compounds with 4 or...,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/PDE5A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/POU Domain Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphodiesterase 5 Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins B-raf,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/blebbistatin,
http://linkedlifedata.com/resource/pubmed/chemical/myosin light chain 2,
http://linkedlifedata.com/resource/pubmed/chemical/transcription factor Brn-2
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1878-3686
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
18
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-57
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pubmed:meshHeading |
pubmed-meshheading:21215707-Animals,
pubmed-meshheading:21215707-Calcimycin,
pubmed-meshheading:21215707-Calcium,
pubmed-meshheading:21215707-Cardiac Myosins,
pubmed-meshheading:21215707-Cell Line, Tumor,
pubmed-meshheading:21215707-Cell Movement,
pubmed-meshheading:21215707-Cell Proliferation,
pubmed-meshheading:21215707-Cyclic GMP,
pubmed-meshheading:21215707-Cyclic Nucleotide Phosphodiesterases, Type 5,
pubmed-meshheading:21215707-Down-Regulation,
pubmed-meshheading:21215707-Gene Expression,
pubmed-meshheading:21215707-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:21215707-Heterocyclic Compounds with 4 or More Rings,
pubmed-meshheading:21215707-Homeodomain Proteins,
pubmed-meshheading:21215707-Humans,
pubmed-meshheading:21215707-Lung Neoplasms,
pubmed-meshheading:21215707-Melanoma,
pubmed-meshheading:21215707-Mice,
pubmed-meshheading:21215707-Mice, Nude,
pubmed-meshheading:21215707-Myosin Light Chains,
pubmed-meshheading:21215707-Neoplasm Invasiveness,
pubmed-meshheading:21215707-POU Domain Factors,
pubmed-meshheading:21215707-Phosphodiesterase 5 Inhibitors,
pubmed-meshheading:21215707-Phosphorylation,
pubmed-meshheading:21215707-Promoter Regions, Genetic,
pubmed-meshheading:21215707-Protein Binding,
pubmed-meshheading:21215707-Protein Kinase Inhibitors,
pubmed-meshheading:21215707-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:21215707-RNA, Small Interfering,
pubmed-meshheading:21215707-Transplantation, Heterologous
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pubmed:year |
2011
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pubmed:articleTitle |
Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A.
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pubmed:affiliation |
The Institute of Cancer Research, Signal Transduction Team, Section of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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