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Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations
http://hdl.handle.net/2297/32869
http://hdl.handle.net/2297/3286984bd7a90-9e01-45c4-8a81-60695e8b1753
名前 / ファイル | ライセンス | アクション |
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CA-PR-YAMADA-T-4427.pdf (1.0 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2017-10-05 | |||||
タイトル | ||||||
タイトル | Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Yamada, Tadaaki
× Yamada, Tadaaki× Takeuchi, Shinji× Fujita, Naoya× Nakamura, Akito× Wang, Wei× Li, Qi× Oda, Makoto× Mitsudomi, Tetsuya× Yatabe, Yasushi× Sekido, Yoshitaka× Yoshida, Junji× Higashiyama, Masahiko× Noguchi, Masayuki× Uehara, Hisanori× Nishioka, Yasuhiko× Sone, Saburo× Yano, Seiji |
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書誌情報 |
Oncogene 巻 32, 号 37, p. 4427-4435, 発行日 2013-09-12 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0950-9232 | |||||
NCID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10687380 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/onc.2012.446 | |||||
出版者 | ||||||
出版者 | Nature Publishing Group | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Despite initial dramatic response, epidermal growth factor receptor (EGFR) mutant lung cancer patients always acquire resistance to EGFR-tyrosine kinase inhibitors (TKIs). Gatekeeper T790M mutation in EGFR is the most prevalent genetic alteration underlying acquired resistance to EGFR-TKI, and EGFR mutant lung cancer cells are reported to be addictive to EGFR/Akt signaling even after acquired T790M mutation. Here, we focused on Akt kinase-interacting protein1 (Aki1), a scaffold protein of PI3K (phosphoinositide 3-kinase)/PDK1 (3-phosphoinositide-dependent protein kinase)/Akt that determines receptor signal selectivity for non-mutated EGFR, and assessed its role in EGFR mutant lung cancer with or without gatekeeper T790M mutation. Cell line-based assays showed that Aki1 constitutively associates with mutant EGFR in lung cancer cells with (H1975) or without (PC-9 and HCC827) T790M gatekeeper mutation. Silencing of Aki1 induced apoptosis of EGFR mutant lung cancer cells. Treatment with Aki1 siRNA dramatically inhibited growth of H1975 cells in a xenograft model. Moreover, silencing of Aki1 further potentiated growth inhibitory effect of new generation EGFR-TKIs against H1975 cells in vitro. Aki1 was frequently expressed in tumor cells of EGFR mutant lung cancer patients (53/56 cases), including those with acquired resistance to EGFR-TKI treatment (7/7 cases). Our data suggest that Aki1 may be a critical mediator of survival signaling from mutant EGFR to Akt, and may therefore be an ideal target for EGFR mutant lung cancer patients, especially those with acquired EGFR-TKI resistance due to EGFR T790M gatekeeper mutation.Oncogene advance online publication, 8 October 2012; doi:10.1038/onc.2012.446. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | In Press → 発行後6か月より全文を公開. | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa |