Source:http://linkedlifedata.com/resource/pubmed/id/16247454
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2006-3-2
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| pubmed:abstractText |
Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express signaling-incompetent beta1B variants. Cells grown on fibronectin, collagen-III, beta1-integrin-IgG or poly-l-lysine were exposed to 0-6 Gy X-rays in presence or depletion of growth factors and phosphatidylinositol-3 kinase (PI3K) inhibitors (LY294002, wortmannin). In order to test the relevance of these findings in tumor cells, human A-172 glioma cells were examined under the same conditions after siRNA-mediated silencing of beta1-integrins. We found that beta1A-integrin-mediated adhesion to fibronectin, collagen-III or beta1-IgG was essential for cell survival after radiation-induced genotoxic injury. Mediated by PI3K, pro-survival beta1A-integrin/Akt signaling was critically involved in this process. Additionally, the beta1-integrin downstream targets p130Cas and paxillin-impaired survival-regulating PI3K-dependent JNK. In A-172 glioma cells, beta1-integrin knockdown and PI3K inhibition confirmed the central role of beta1-integrins in Akt- and p130Cas/paxillin-mediated prosurvival signaling. These findings suggest beta1-integrins as critical regulators of cell survival after radiation-induced genotoxic injury. Elucidation of the molecular circuitry of prosurvival beta1-integrin-mediated signaling in tumor cells may promote the development of innovative molecular-targeted therapeutic antitumor strategies.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD29,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0950-9232
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
2
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| pubmed:volume |
25
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1378-90
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| pubmed:dateRevised |
2010-4-12
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| pubmed:meshHeading |
pubmed-meshheading:16247454-Animals,
pubmed-meshheading:16247454-Antigens, CD29,
pubmed-meshheading:16247454-Brain Neoplasms,
pubmed-meshheading:16247454-Cell Adhesion,
pubmed-meshheading:16247454-Cell Culture Techniques,
pubmed-meshheading:16247454-Cell Survival,
pubmed-meshheading:16247454-Extracellular Matrix Proteins,
pubmed-meshheading:16247454-Fibroblasts,
pubmed-meshheading:16247454-Fibronectins,
pubmed-meshheading:16247454-Glioma,
pubmed-meshheading:16247454-Growth Substances,
pubmed-meshheading:16247454-Humans,
pubmed-meshheading:16247454-Mice,
pubmed-meshheading:16247454-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16247454-RNA, Small Interfering,
pubmed-meshheading:16247454-Radiation Injuries,
pubmed-meshheading:16247454-Signal Transduction,
pubmed-meshheading:16247454-Tumor Cells, Cultured,
pubmed-meshheading:16247454-X-Rays
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| pubmed:year |
2006
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| pubmed:articleTitle |
beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury.
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| pubmed:affiliation |
OncoRay -- Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse, Dresden, Germany. Nils.Cordes@mailbox.tu-dresden.de
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| pubmed:publicationType |
Journal Article
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