{"created":"2024-12-12T01:20:24.287760+00:00","id":2009169,"links":{},"metadata":{"_buckets":{"deposit":"01cf1073-041b-4a34-9111-a3167c3f66e3"},"_deposit":{"created_by":7,"id":"2009169","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2009169"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02009169","sets":["1713853213384:1713853295607"]},"author_link":["852"],"control_number":"2009169","item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-07-27","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"32","bibliographicPageEnd":"19445","bibliographicPageStart":"19435","bibliographicVolumeNumber":"117","bibliographic_titles":[{"bibliographic_title":"Proceedings of the National Academy of Sciences of the United States of America","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The Ras/RAF/MEK/ERK pathway is an essential signaling cascade for various refractory cancers, such as those with mutant KRAS (mKRAS) and BRAF (mBRAF). However, there are unsolved ambiguities underlying mechanisms for this growth signaling thereby creating therapeutic complications. This study shows that a vital component of the pathway CRAF is directly impacted by an end product of the cascade, glutathione transferases (GST) P1 (GSTP1), driving a previously unrecognized autocrine cycle that sustains proliferation of mKRAS and mBRAF cancer cells, independent of oncogenic stimuli. The CRAF interaction with GSTP1 occurs at its N-terminal regulatory domain, CR1 motif, resulting in its stabilization, enhanced dimerization, and augmented catalytic activity. Consistent with the autocrine cycle scheme, silencing GSTP1 brought about significant suppression of proliferation of mKRAS and mBRAF cells in vitro and suppressed tumorigenesis of the xenografted mKRAS tumor in vivo. GSTP1 knockout mice showed significantly impaired carcinogenesis of mKRAS colon cancer. Consequently, hindering the autocrine loop by targeting CRAF/GSTP1 interactions should provide innovative therapeutic modalities for these cancers.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"National Academy of Sciences","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"10916490","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"AA11726874","subitem_source_identifier_type":"NCID"}]},"item_10001_version_type_20":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1715043197608":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access"}]},"item_1722929371688":{"attribute_name":"出版社版DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"10.1073/pnas.2000361117"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1073/pnas.2000361117","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"367314"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"ニイツ, ヨウシロウ","creatorNameLang":"ja"},{"creatorName":"ニイツ, ヨウシロウ","creatorNameLang":"ja-Kana"},{"creatorName":"Niitsu, Yoshiro","creatorNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"佐藤, 康史","creatorNameLang":"ja"},{"creatorName":"サトウ, ヤスシ","creatorNameLang":"ja-Kana"},{"creatorName":"Sato, Yasushi","creatorNameLang":"en"}],"familyNames":[{"familyName":"佐藤","familyNameLang":"ja"},{"familyName":"サトウ","familyNameLang":"ja-Kana"},{"familyName":"Sato","familyNameLang":"en"}],"givenNames":[{"givenName":"康史","givenNameLang":"ja"},{"givenName":"ヤスシ","givenNameLang":"ja-Kana"},{"givenName":"Yasushi","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"852","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"321662/profile-ja.html","nameIdentifierScheme":"徳島大学 教育研究者総覧","nameIdentifierURI":"http://pub2.db.tokushima-u.ac.jp/ERD/person/321662/profile-ja.html"}]},{"creatorNames":[{"creatorName":"タカナシ, クニヒロ","creatorNameLang":"ja"},{"creatorName":"タカナシ, クニヒロ","creatorNameLang":"ja-Kana"},{"creatorName":"Takanashi, Kunihiro","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"ハヤシ, ツヨシ","creatorNameLang":"ja"},{"creatorName":"ハヤシ, ツヨシ","creatorNameLang":"ja-Kana"},{"creatorName":"Hayashi, Tsuyoshi","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"クボ ビルカワ, ナオコ","creatorNameLang":"ja"},{"creatorName":"クボ ビルカワ, ナオコ","creatorNameLang":"ja-Kana"},{"creatorName":"Kubo-Birukawa, Naoko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"シミズ, フミコ","creatorNameLang":"ja"},{"creatorName":"シミズ, フミコ","creatorNameLang":"ja-Kana"},{"creatorName":"Shimizu, Fumiko","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"フジタニ, ナオキ","creatorNameLang":"ja"},{"creatorName":"フジタニ, ナオキ","creatorNameLang":"ja-Kana"},{"creatorName":"Fujitani, Naoki","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"シモヤマ, ライ","creatorNameLang":"ja"},{"creatorName":"シモヤマ, ライ","creatorNameLang":"ja-Kana"},{"creatorName":"Shimoyama, Rai","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"クキツ, タケヒロ","creatorNameLang":"ja"},{"creatorName":"クキツ, タケヒロ","creatorNameLang":"ja-Kana"},{"creatorName":"Kukitsu, Takehiro","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"クラタ, ワタル","creatorNameLang":"ja"},{"creatorName":"クラタ, ワタル","creatorNameLang":"ja-Kana"},{"creatorName":"Kurata, Wataru","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"タシロ, ヤスユキ","creatorNameLang":"ja"},{"creatorName":"タシロ, ヤスユキ","creatorNameLang":"ja-Kana"},{"creatorName":"Tashiro, Yasuyuki","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Listowsky, Irving","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2021-09-07"}],"displaytype":"detail","filename":"pnas_117_32_19435.pdf","filesize":[{"value":"1.91 MB"}],"format":"application/pdf","licensetype":"license_5","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://tokushima-u.repo.nii.ac.jp/record/2009169/files/pnas_117_32_19435.pdf"},"version_id":"1b9a642f-b217-4bfa-b3f4-364800772cf4"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"mKRAS and mBRAF cancers","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"autocrine growth cycle","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CRAF/GSTP1 complex","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"refractory cancers","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"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":"A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1713853295607"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2021-09-07"},"publish_date":"2021-09-07","publish_status":"0","recid":"2009169","relation_version_is_last":true,"title":["A CRAF/glutathione-S-transferase P1 complex sustains autocrine growth of cancers with KRAS and BRAF mutations"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2025-01-29T12:22:20.678654+00:00"}