{"created":"2023-07-27T06:39:08.553422+00:00","id":27471,"links":{},"metadata":{"_buckets":{"deposit":"c62116b5-dc24-45de-a14a-d99d7da4506b"},"_deposit":{"created_by":3,"id":"27471","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"27471"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00027471","sets":["1777:1778:1779"]},"author_link":["47821","47827","1175","47829","47819","141","47826","47830","47825","47834","85","47833","47828","47823","47822","47820","47824","47831","47832"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-08-13","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"13076","bibliographicVolumeNumber":"5","bibliographic_titles":[{"bibliographic_title":"Scientific Reports"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"There is a high death rate of lung cancer patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective in some lung adenocarcinoma patients with EGFR mutations. However, a significant number of patients show primary and acquire resistance to EGFR-TKIs. Although the Akt kinase is commonly activated due to various resistance mechanisms, the key targets of Akt remain unclear. Here, we show that the Akt-β-catenin pathway may be a common resistance mechanism. We analyzed gene expression profiles of gefitinib-resistant PC9M2 cells that were derived from gefitinib-sensitive lung cancer PC9 cells and do not have known resistance mechanisms including EGFR mutation T790M. We found increased expression of Axin, a β-catenin target gene, increased phosphorylation of Akt and GSK3, accumulation of β-catenin in the cytoplasm/nucleus in PC9M2 cells. Both knockdown of β-catenin and treatment with a β-catenin inhibitor at least partially restored gefitinib sensitivity to PC9M2 cells. Lung adenocarcinoma tissues derived from gefitinib-resistant patients displayed a tendency to accumulate β-catenin in the cytoplasm. We provide a rationale for combination therapy that includes targeting of the Akt-β-catenin pathway to improve the efficacy of EGFR-TKIs.","subitem_description_type":"Abstract"}]},"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":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1038/srep13076","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"2045-2322","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_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Nakata, Asuka"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Yoshida, Ryo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yamaguchi, Rui"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yamauchi, Mai"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tamada, Yoshinori"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Fujita, Andre"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Shimamura, Teppei"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Imoto, Seiya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Higuchi, Tomoyuki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nomura, Masaharu"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Kimura, Tatsuo"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nokihara, Hiroshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Higashiyama, Masahiko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Kondoh, Kazuya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nishihara, Hiroshi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tojo, Arinobu"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yano, Seiji"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Miyano, Satoru"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Gotoh, Noriko"}],"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-GOTO-N-13076.pdf","filesize":[{"value":"659.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"CA-PR-GOTO-N-13076.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/27471/files/CA-PR-GOTO-N-13076.pdf"},"version_id":"55159cc2-1234-4f0f-99cd-a82a8918ff8b"}]},"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":"Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs"}]},"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":"27471","relation_version_is_last":true,"title":["Elevated β-catenin pathway as a novel target for patients with resistance to EGF receptor targeting drugs"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-27T21:05:53.238076+00:00"}