|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2005-3-22
|
|
pubmed:abstractText |
Osteosarcoma is the most frequent primary malignant tumor of bone with a high propensity for metastasis. We have previously showed that ezrin expression is necessary for metastatic behavior in a murine model of osteosarcoma (K7M2). In this study, we found that a mechanism of ezrin-related metastatic behavior is linked to an Akt-dependent mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (S6K1)/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) pathway. Suppression of ezrin expression either by antisense transfection or by small interfering RNAs or disruption of ezrin function by transfection of a dominant-negative ezrin-T567A mutant led to decreased expression and decreased phosphorylation of both S6K1 and 4E-BP1. Proteosomal inhibition by MG132 reversed antisense-mediated decrease of S6K1 and 4E-BP1 protein expression, but failed to affect the effect of ezrin on phosphorylation of S6K1 and 4E-BP1. Blockade of the mTOR pathway with rapamycin or its analog, cell cycle inhibitor-779 led to significant inhibition of experimental lung metastasis in vivo. These results suggest that blocking the mTOR/S6K1/4E-BP1 pathway may be an appropriate target for strategies to reduce tumor cell metastasis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Eif4ebp1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Antisense,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 70-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/ezrin,
http://linkedlifedata.com/resource/pubmed/chemical/temsirolimus
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0008-5472
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
65
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2406-11
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:15781656-Animals,
pubmed-meshheading:15781656-Bone Neoplasms,
pubmed-meshheading:15781656-Carrier Proteins,
pubmed-meshheading:15781656-Cytoskeletal Proteins,
pubmed-meshheading:15781656-Female,
pubmed-meshheading:15781656-Mice,
pubmed-meshheading:15781656-Mice, SCID,
pubmed-meshheading:15781656-Osteosarcoma,
pubmed-meshheading:15781656-Phosphoproteins,
pubmed-meshheading:15781656-Phosphorylation,
pubmed-meshheading:15781656-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15781656-Proto-Oncogene Proteins,
pubmed-meshheading:15781656-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15781656-RNA, Antisense,
pubmed-meshheading:15781656-RNA, Small Interfering,
pubmed-meshheading:15781656-Ribosomal Protein S6 Kinases, 70-kDa,
pubmed-meshheading:15781656-Sirolimus,
pubmed-meshheading:15781656-Transfection
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma.
|
|
pubmed:affiliation |
Molecular Oncology Section, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1106, USA.
|
|
pubmed:publicationType |
Journal Article
|
