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dc.contributor.author | Hamaoka, Yuho | en |
dc.contributor.author | Negishi, Manabu | en |
dc.contributor.author | Katoh, Hironori | en |
dc.contributor.alternative | 濱岡, 裕穂 | ja |
dc.contributor.alternative | 根岸, 学 | ja |
dc.contributor.alternative | 加藤, 裕教 | ja |
dc.date.accessioned | 2018-03-20T01:25:57Z | - |
dc.date.available | 2018-03-20T01:25:57Z | - |
dc.date.issued | 2016-08 | - |
dc.identifier.issn | 1873-3913 | - |
dc.identifier.uri | http://hdl.handle.net/2433/230208 | - |
dc.description.abstract | EphA2, a member of the Eph receptor tyrosine kinases, is frequently overexpressed in a variety of malignancies, including glioblastoma, and its expression is correlated with poor prognosis. EphA2 acts as a tumor promoter through a ligand ephrin-independent mechanism, which requires phosphorylation of EphA2 on serine 897 (S897), leading to increased cell migration and invasion. In this study, we show that ligand-independent EphA2 signaling occurs downstream of the MEK/ERK/RSK pathway and mediates epidermal growth factor (EGF)-induced cell proliferation in glioblastoma cells. Suppression of EphA2 expression by long-term exposure to ligand ephrinA1 or EphA2-targeted shRNA inhibited EGF-induced cell proliferation. Stimulation of the cells with EGF induced EphA2 S897 phosphorylation, which was suppressed by MEK and RSK inhibitors, but not by phosphatidylinositol 3-kinase (PI3K) and Akt inhibitors. The RSK inhibitor or RSK2-targeted shRNA also suppressed EGF-induced cell proliferation. Furthermore, overexpression of wild-type EphA2 promoted cell proliferation without EGF stimulation, whereas overexpression of EphA2-S897A mutant suppressed EGF- or RSK2-induced proliferation. Taken together, these results suggest that EphA2 is a key downstream target of the MEK/ERK/RSK signaling pathway in the regulation of glioblastoma cell proliferation. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier Inc. | en |
dc.rights | © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | en |
dc.rights | The full-text file will be made open to the public on 1 August 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. | en |
dc.rights | この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 | ja |
dc.rights | This is not the published version. Please cite only the published version. | en |
dc.subject | EphA2 | en |
dc.subject | RSK | en |
dc.subject | EGF | en |
dc.subject | Cell proliferation | en |
dc.subject | Glioblastoma | en |
dc.title | EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Cellular Signalling | en |
dc.identifier.volume | 28 | - |
dc.identifier.issue | 8 | - |
dc.identifier.spage | 937 | - |
dc.identifier.epage | 945 | - |
dc.relation.doi | 10.1016/j.cellsig.2016.04.009 | - |
dc.textversion | author | - |
dc.address | Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University | en |
dc.address | Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University・Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University | en |
dc.address | Laboratory of Molecular Neurobiology, Graduate School of Pharmaceutical Sciences, Kyoto University・Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University | en |
dc.identifier.pmid | 27132626 | - |
dcterms.accessRights | open access | - |
datacite.date.available | 2016-08-01 | - |
出現コレクション: | 学術雑誌掲載論文等 |
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