{"created":"2023-07-27T06:39:07.906666+00:00","id":27459,"links":{},"metadata":{"_buckets":{"deposit":"d008430b-93e3-4e43-b2cd-145d77f01859"},"_deposit":{"created_by":3,"id":"27459","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"27459"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00027459","sets":["1777:1778:1779"]},"author_link":["47794","47787","47786","186","47793","141","47791","47788","47796","1410","1130","565","47792","47795","47790","47789","440"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2013-09-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"37","bibliographicPageEnd":"4435","bibliographicPageStart":"4427","bibliographicVolumeNumber":"32","bibliographic_titles":[{"bibliographic_title":"Oncogene"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"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.","subitem_description_type":"Abstract"}]},"item_4_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"In Press → 発行後6か月より全文を公開.","subitem_description_type":"Other"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Nature Publishing Group"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/onc.2012.446","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_11":{"attribute_name":"NCID","attribute_value_mlt":[{"subitem_source_identifier":"AA10687380","subitem_source_identifier_type":"NCID"}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0950-9232","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Yamada, Tadaaki"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Takeuchi, Shinji"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Fujita, Naoya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nakamura, Akito"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Wang, Wei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Li, Qi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Oda, Makoto"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Mitsudomi, Tetsuya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yatabe, Yasushi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sekido, Yoshitaka"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yoshida, Junji"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Higashiyama, Masahiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Noguchi, Masayuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Uehara, Hisanori"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nishioka, Yasuhiko"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Sone, Saburo"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Yano, Seiji"}],"nameIdentifiers":[{},{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-05"}],"displaytype":"detail","filename":"CA-PR-YAMADA-T-4427.pdf","filesize":[{"value":"1.0 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"CA-PR-YAMADA-T-4427.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/27459/files/CA-PR-YAMADA-T-4427.pdf"},"version_id":"a2d0d490-d953-4521-97eb-42538b86b527"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations"}]},"item_type_id":"4","owner":"3","path":["1779"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-05"},"publish_date":"2017-10-05","publish_status":"0","recid":"27459","relation_version_is_last":true,"title":["Akt kinase-interacting protein1, a novel therapeutic target for lung cancer with EGFR-activating and gatekeeper mutations"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-27T21:06:02.778104+00:00"}