{"created":"2023-06-19T07:25:19.825745+00:00","id":13031,"links":{},"metadata":{"_buckets":{"deposit":"cd2549b4-8b68-4ede-924a-8960b1f252d9"},"_deposit":{"created_by":4,"id":"13031","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"13031"},"status":"published"},"_oai":{"id":"oai:gifu-pu.repo.nii.ac.jp:00013031","sets":["147:228"]},"author_link":["18205","18203","18204"],"item_1_biblio_info_14":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2016-06-30","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"10","bibliographicPageStart":"1","bibliographicVolumeNumber":"65","bibliographic_titles":[{"bibliographic_title":"岐阜薬科大学紀要"},{"bibliographic_title":"The annual proceedings of Gifu Pharmaceutical University","bibliographic_titleLang":"en"}]}]},"item_1_creator_6":{"attribute_name":"著者名(日)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"五十里 , 彰"}],"nameIdentifiers":[{"nameIdentifier":"18203","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_7":{"attribute_name":"著者名よみ","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"イカリ, アキラ"}],"nameIdentifiers":[{"nameIdentifier":"18204","nameIdentifierScheme":"WEKO"}]}]},"item_1_creator_8":{"attribute_name":"著者名(英)","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"IKARI, Akira ","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"18205","nameIdentifierScheme":"WEKO"}]}]},"item_1_description_1":{"attribute_name":"ページ属性","attribute_value_mlt":[{"subitem_description":"P(論文)","subitem_description_type":"Other"}]},"item_1_description_11":{"attribute_name":"抄録(日)","attribute_value_mlt":[{"subitem_description":"肺がんによる死亡者数は増加傾向にあり、新たな治療標的の同定と治療法の開発が必要である。これまでに著者ら\nは、細胞間接着を構成するクローディン-2 が正常肺組織に発現しないが、腺がん組織に高発現することを見出している。\n肺腺がん細胞におけるクローディン-2 の発現をノックダウンすると細胞増殖能が低下したため、クローディン-2 による\n細胞増殖の調節機構を検討した。また、クローディン-2 が肺腺がんの治療標的になると考えられたため、クローディン-2\n発現を抑制する化合物を探索した。その結果、増殖期の細胞においてクローディン-2 は核内とタイトジャンクションに\n分布し、細胞周期調節因子のZO-1 associated nucleic acid binding protein（ZONAB）と結合することを解明した。クローデ\nィン-2 の発現をノックダウンすると、ZONAB の発現量が低下してG1 期の細胞の割合が増加した。クローディン-2 の核\n移行機序を検討し、208 番目のセリン残基のリン酸化が一部関与することを突き止めた。また、クローディン-2 指向性ペ\nプチドがタイトジャンクションから細胞質内へのクローディン-2 の移行を介してネクローシスによる細胞死を誘導する\nことを発見した。クローディン-2 はクラスリン依存性エンドサイトーシスによって細胞質内へ移行し、リソソームで分\n解された。フラボノイドのケルセチンはクローディン-2 の転写活性を低下させず、miR-16 マイクロRNA の発現誘導を介\nしてクローディン-2 mRNA 量の安定性を低下させ、その発現量を低下させた。クローディン-2 を起点とするがん化機構\nの解明とその阻害剤の探索は、肺腺がんの新たな治療法の開発につながると期待できる。","subitem_description_type":"Other"}]},"item_1_description_12":{"attribute_name":"抄録(英)","attribute_value_mlt":[{"subitem_description":"The mortality associated with lung cancer has been increasing; consequently, novel therapeutic targets need to be\nidentified and novel therapeutic methods need to be developed. We recently reported that claudin-2, a component of the tight junction\n(TJ), was expressed in human lung adenocarcinoma, whereas it was absent from normal lung tissues. Knockdown of claudin-2 in\nlung adenocarcinoma cells decreased their proliferation. Therefore, we examined the mechanism underlying the regulation of cell\nproliferation by claudin-2. Moreover, we sought out compounds that can decrease claudin-2 expression. We found that claudin-2 was\ndistributed both in the nucleus and in the TJ in proliferating cells and was bound with the ZO-1 associated nucleic acid binding\n(ZONAB) protein, which controls cell-cycle regulator expression. shRNA-mediated knockdown of claudin-2 decreased ZONAB\nexpression and increased the proportion of cells in the G1 phase of the cell cycle. Moreover, we examined the nuclear trafficking of\nclaudin-2 and found that this trafficking was regulated in part by the phosphorylation of claudin-2 at Ser208. The short peptide,\nDFYSP, whose sequence mimics the second extracellular loop of claudin-2, caused claudin-2 to be trafficked from the TJ to cytosol,\nincreased lysosomal degradation of claudin-2, and induced necrotic cell death. Transport of claudin-2 to the cytosol was mediated via\na clathrin-dependent endocytosis pathway. Quercetin, a flavonoid, decreased claudin-2 expression through the induction of miR-16\nand a decrease in the stability of claudin-2 mRNA, although it did not inhibit the transcriptional activity of the claudin-2 gene. The\nclarification of the involvement of claudin-2 in the molecular mechanism underlying carcinogenesis and the identification of\nclaudin-2 inhibitors will lead to the development of novel agents for the treatment of lung adenocarcinoma.","subitem_description_type":"Other"}]},"item_1_source_id_13":{"attribute_name":"雑誌書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AA1258935X","subitem_source_identifier_type":"NCID"}]},"item_1_text_10":{"attribute_name":"著者所属(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Laboratory of Biochemistry, Gifu Pharmaceutical University"}]},"item_1_text_2":{"attribute_name":"記事種別(日)","attribute_value_mlt":[{"subitem_text_value":"総説"}]},"item_1_text_3":{"attribute_name":"記事種別(英)","attribute_value_mlt":[{"subitem_text_language":"en","subitem_text_value":"Review"}]},"item_1_text_9":{"attribute_name":"著者所属(日)","attribute_value_mlt":[{"subitem_text_value":"岐阜薬科大学生命薬学大講座生化学研究室"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-07-29"}],"displaytype":"detail","filename":"no65 2-11.pdf","filesize":[{"value":"1.0 MB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"no65 2-11","url":"https://gifu-pu.repo.nii.ac.jp/record/13031/files/no65 2-11.pdf"},"version_id":"8c3be56a-4a96-417b-a068-b23045eecb8b"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"肺がん","subitem_subject_scheme":"Other"},{"subitem_subject":"タイトジャンクション","subitem_subject_scheme":"Other"},{"subitem_subject":"クローディン","subitem_subject_scheme":"Other"},{"subitem_subject":"核移行","subitem_subject_scheme":"Other"},{"subitem_subject":"マイクロRNA","subitem_subject_scheme":"Other"},{"subitem_subject":"lung cancer","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"tight junction","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"claudin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"nuclear trafficking","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"microRNA","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"細胞間接着を起点とするがん化機構に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"細胞間接着を起点とするがん化機構に関する研究"},{"subitem_title":"Molecular Mechanism Underlying Carcinogenesis Caused by Abnormal Cell–cell Contact","subitem_title_language":"en"}]},"item_type_id":"1","owner":"4","path":["228"],"pubdate":{"attribute_name":"公開日","attribute_value":"2016-07-29"},"publish_date":"2016-07-29","publish_status":"0","recid":"13031","relation_version_is_last":true,"title":["細胞間接着を起点とするがん化機構に関する研究"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2023-06-19T08:59:40.732248+00:00"}