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Engagement of Overexpressed Her2 with GEP100 Induces Autonomous Invasive Activities and Provides a Biomarker for Metastases of Lung Adenocarcinoma
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| Title: | Engagement of Overexpressed Her2 with GEP100 Induces Autonomous Invasive Activities and Provides a Biomarker for Metastases of Lung Adenocarcinoma |
| Authors: | Menju, Toshi Browse this author | | Hashimoto, Shigeru Browse this author | | Hashimoto, Ari Browse this author | | Otsuka, Yutaro Browse this author | | Handa, Haruka Browse this author | | Ogawa, Eiji Browse this author | | Toda, Yoshinobu Browse this author | | Wada, Hiromi Browse this author | | Date, Hiroshi Browse this author | | Sabe, Hisataka Browse this author →KAKEN DB |
| Issue Date: | 22-Sep-2011 |
| Publisher: | Public Library of Science |
| Journal Title: | PLoS One |
| Volume: | 6 |
| Issue: | 9 |
| Start Page: | e25301 |
| Publisher DOI: | 10.1371/journal.pone.0025301 |
| 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. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/47384 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 佐邊 壽孝
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