論文 - 詳細
| RRC ID | 68642 |
|---|---|
| 著者 | Menju T, Hashimoto S, Hashimoto A, Otsuka Y, Handa H, Ogawa E, Toda Y, Wada H, Date H, Sabe H. |
| タイトル | Engagement of overexpressed Her2 with GEP100 induces autonomous invasive activities and provides a biomarker for metastases of lung adenocarcinoma. |
| ジャーナル | PLoS One |
| Abstract |
Overexpression of Her2/ErbB2/Neu in cancer is often correlated with recurrent distant metastasis, although the mechanism still remains largely elusive. We have previously shown that EGFR, when tyrosine-phosphorylated, binds to GEP100/BRAG2 to activate Arf6, which induces cancer invasion and metastasis. We now show that overexpressed Her2 in lung adenocarcinoma cells also employs GEP100. Like EGFR-GEP100 binding, this association is primarily mediated by the pleckstrin homology (PH) domain of GEP100 and Tyr1139/Tyr1196 of Her2. Tyr1139/Tyr1196 are autonomously phosphorylated, when Her2 is overexpressed. Accordingly, invasive activities mediated by the Her2-GEP100 pathway are not dependent on external factors. Blocking Her2-GEP100 binding, as well as its signaling pathway all inhibit cancer invasive activities. Moreover, our clinical study indicates that co-overexpression of Her2 with GEP100 in primary lung adenocarcinomas of patients is correlated with the presence of their node-metastasis with a statistical significance. Since the GEP100 PH domain interacts with both Her2 and EGFR, targeting this domain may provide novel cancer therapeutics. |
| 巻・号 | 6(9) |
| ページ | e25301 |
| 公開日 | 2011-1-1 |
| DOI | 10.1371/journal.pone.0025301 |
| PII | PONE-D-11-07424 |
| PMID | 21966491 |
| PMC | PMC3178645 |
| MeSH | Adaptor Proteins, Vesicular Transport / genetics Adaptor Proteins, Vesicular Transport / metabolism Adenocarcinoma / genetics Adenocarcinoma / metabolism* Adenocarcinoma of Lung Cell Line GTPase-Activating Proteins / genetics GTPase-Activating Proteins / metabolism Glutathione Transferase / genetics Glutathione Transferase / metabolism Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Humans Immunoblotting Immunohistochemistry Immunoprecipitation In Vitro Techniques Lung Neoplasms / genetics Lung Neoplasms / metabolism* Neoplasm Metastasis / diagnosis* Neoplasm Metastasis / genetics* Protein Binding RNA Interference Receptor, ErbB-2 / genetics Receptor, ErbB-2 / metabolism* |
| IF | 2.74 |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Lu99(RCB1900) PC-9(RCB4455) |