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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2008-2-28
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pubmed:abstractText |
Signals from fibronectin-binding integrins promote neural crest cell motility during development in part through protein-tyrosine kinase (PTK) activation. Neuroblastoma (NB) is a neural crest malignancy with high metastatic potential. We find that alpha4 and alpha5 integrins are present in late-stage NB tumors and cell lines derived thereof. To determine the signaling connections promoting either alpha4beta1- or alpha5beta1-initiated NB cell motility, pharmacological, dominant negative and short-hairpin RNA (shRNA) inhibitory approaches were undertaken. shRNA knockdown revealed that alpha5beta1-stimulated NB motility is dependent upon focal adhesion kinase (FAK) PTK, Src PTK and p130Cas adapter protein expression. Cell reconstitution showed that FAK catalytic activity is required for alpha5beta1-stimulated Src activation in part through direct FAK phosphorylation of Src at Tyr-418. Alternatively, alpha4beta1-stimulated NB cell motility is dependent upon Src and p130Cas but FAK is not essential. Catalytically inactive receptor protein-tyrosine phosphatase-alpha overexpression inhibited alpha4beta1-stimulated NB motility and Src activation consistent with alpha4-regulated Src activity occurring through Src Tyr-529 dephosphorylation. In alpha4 shRNA-expressing NB cells, alpha4beta1-stimulated Src activation and NB cell motility were rescued by wild type but not cytoplasmic domain-truncated alpha4 re-expression. These studies, supported by results using reconstituted fibroblasts, reveal that alpha4beta1-mediated Src activation is mechanistically distinct from FAK-mediated Src activation during alpha5beta1-mediated NB migration and support the evaluation of inhibitors to alpha4, Src and FAK in the control of NB tumor progression.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-10218097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-11668592,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12221126,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12234367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12244123,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12515828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12612655,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12640026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12695503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-12711704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-14657279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15459662,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-1547502,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15592458,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15688067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15803131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15845350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-15946252,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-16227616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-16397500,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-16507567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-16919435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-7529876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-7539441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17828307-9758701
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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 |
Feb
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pubmed:issn |
1476-5594
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pubmed:author |
pubmed-author:Bernard-TrifiloJ AJA,
pubmed-author:ChenMM,
pubmed-author:CheungN-KvNK,
pubmed-author:LieAA,
pubmed-author:Ma S SSS,
pubmed-author:MielgoAA,
pubmed-author:MikolonDD,
pubmed-author:MitraS KSK,
pubmed-author:PallenC JCJ,
pubmed-author:SchlaepferD DDD,
pubmed-author:StupackD GDG,
pubmed-author:UryuSS,
pubmed-author:WuLL
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pubmed:issnType |
Electronic
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pubmed:day |
28
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1439-48
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pubmed:dateRevised |
2011-3-9
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pubmed:meshHeading |
pubmed-meshheading:17828307-Cell Movement,
pubmed-meshheading:17828307-Enzyme Activation,
pubmed-meshheading:17828307-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:17828307-Humans,
pubmed-meshheading:17828307-Integrin alpha4beta1,
pubmed-meshheading:17828307-Integrin alpha5beta1,
pubmed-meshheading:17828307-Neuroblastoma,
pubmed-meshheading:17828307-Protein Structure, Tertiary,
pubmed-meshheading:17828307-Proto-Oncogene Proteins pp60(c-src),
pubmed-meshheading:17828307-Tumor Cells, Cultured
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pubmed:year |
2008
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pubmed:articleTitle |
Distinct FAK-Src activation events promote alpha5beta1 and alpha4beta1 integrin-stimulated neuroblastoma cell motility.
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pubmed:affiliation |
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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