2016年8月
EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation
CELLULAR SIGNALLING
- ,
- ,
- 巻
- 28
- 号
- 8
- 開始ページ
- 937
- 終了ページ
- 945
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.cellsig.2016.04.009
- 出版者・発行元
- ELSEVIER SCIENCE INC
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 5897 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. (C) 2016 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.cellsig.2016.04.009
- ISSN : 0898-6568
- eISSN : 1873-3913
- J-Global ID : 201702203512934350
- Web of Science ID : WOS:000378670900016