論文 - 詳細
| RRC ID | 47923 |
|---|---|
| 著者 | Hamaoka Y, Negishi M, Katoh H. |
| タイトル | EphA2 is a key effector of the MEK/ERK/RSK pathway regulating glioblastoma cell proliferation. |
| ジャーナル | Cell Signal |
| 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. |
| 巻・号 | 28(8) |
| ページ | 937-45 |
| 公開日 | 2016-8-1 |
| DOI | 10.1016/j.cellsig.2016.04.009 |
| PII | S0898-6568(16)30095-X |
| PMID | 27132626 |
| MeSH | Brain Neoplasms / enzymology* Brain Neoplasms / pathology* Bromodeoxyuridine / metabolism Cell Line, Tumor Cell Proliferation / drug effects Epidermal Growth Factor / pharmacology Glioblastoma / enzymology* Glioblastoma / pathology* Humans MAP Kinase Signaling System* / drug effects Phosphorylation / drug effects Phosphoserine / metabolism Receptor, EphA2 / metabolism* Ribosomal Protein S6 Kinases, 90-kDa / metabolism* Signal Transduction / drug effects |
| IF | 3.968 |
| 引用数 | 26 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | A172(RCB2530) MKN45(RCB1001) |