{"created":"2024-10-30T10:07:47.157746+00:00","id":2007972,"links":{},"metadata":{"_buckets":{"deposit":"5e3b33fa-bddb-4969-aaec-f2a60e1b7dfe"},"_deposit":{"created_by":7,"id":"2007972","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2007972"},"status":"published"},"_oai":{"id":"oai:tokushima-u.repo.nii.ac.jp:02007972","sets":["1713853213384:1713853295607"]},"author_link":["1256","1211"],"control_number":"2007972","item_10001_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2020-04-04","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"4","bibliographicPageStart":"881","bibliographicVolumeNumber":"12","bibliographic_titles":[{"bibliographic_title":"Cancers","bibliographic_titleLang":"en"}]}]},"item_10001_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Matrix metalloproteinase 3 (MMP3) plays multiple roles in extracellular proteolysis as well as intracellular transcription, prompting a new definition of moonlighting metalloproteinase (MMP), according to a definition of protein moonlighting (or gene sharing), a phenomenon by which a protein can perform more than one function. Indeed, connective tissue growth factor (CTGF, aka cellular communication network factor 2 (CCN2)) is transcriptionally induced as well as cleaved by MMP3. Moreover, several members of the MMP family have been found within tumor-derived extracellular vesicles (EVs). We here investigated the roles of MMP3-rich EVs in tumor progression, molecular transmission, and gene regulation. EVs derived from a rapidly metastatic cancer cell line (LuM1) were enriched in MMP3 and a C-terminal half fragment of CCN2/CTGF. MMP3-rich, LuM1-derived EVs were disseminated to multiple organs through body fluid and were pro-tumorigenic in an allograft mouse model, which prompted us to define LuM1-EVs as oncosomes in the present study. Oncosome-derived MMP3 was transferred into recipient cell nuclei and thereby trans-activated the CCN2/CTGF promoter, and induced CCN2/CTGF production in vitro. TRENDIC and other cis-elements in the CCN2/CTGF promoter were essential for the oncosomal responsivity. The CRISPR/Cas9-mediated knockout of MMP3 showed significant anti-tumor effects such as the inhibition of migration and invasion of tumor cells, and a reduction in CCN2/CTGF promoter activity and fragmentations in vitro. A high expression level of MMP3 or CCN2/CTGF mRNA was prognostic and unfavorable in particular types of cancers including head and neck, lung, pancreatic, cervical, stomach, and urothelial cancers. These data newly demonstrate that oncogenic EVs-derived MMP is a transmissive trans-activator for the cellular communication network gene and promotes tumorigenesis at distant sites.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10001_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI","subitem_publisher_language":"en"}]},"item_10001_rights_15":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).","subitem_rights_language":"en"}]},"item_10001_source_id_9":{"attribute_name":"収録物ID","attribute_value_mlt":[{"subitem_source_identifier":"20726694","subitem_source_identifier_type":"ISSN"}]},"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":"10.3390/cancers12040881"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.3390/cancers12040881","subitem_relation_type_select":"DOI"}}]},"item_1723180141928":{"attribute_name":"EID","attribute_value_mlt":[{"subitem_identifier_type":"URI","subitem_identifier_uri":"365396"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"オクシャ, ユカ","creatorNameLang":"ja"},{"creatorName":"オクシャ, ユカ","creatorNameLang":"ja-Kana"},{"creatorName":"Okusha, Yuka","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"エグチ, タカノリ","creatorNameLang":"ja"},{"creatorName":"エグチ, タカノリ","creatorNameLang":"ja-Kana"},{"creatorName":"Eguchi, Takanori","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Tran, Manh T.","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"ソガワ, チハル","creatorNameLang":"ja"},{"creatorName":"ソガワ, チハル","creatorNameLang":"ja-Kana"},{"creatorName":"Sogawa, Chiharu","creatorNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"吉田, 賀弥","creatorNameLang":"ja"},{"creatorName":"ヨシダ, カヤ","creatorNameLang":"ja-Kana"},{"creatorName":"Yoshida, Kaya","creatorNameLang":"en"}],"familyNames":[{"familyName":"吉田","familyNameLang":"ja"},{"familyName":"ヨシダ","familyNameLang":"ja-Kana"},{"familyName":"Yoshida","familyNameLang":"en"}],"givenNames":[{"givenName":"賀弥","givenNameLang":"ja"},{"givenName":"カヤ","givenNameLang":"ja-Kana"},{"givenName":"Kaya","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1211","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"73175/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/73175/profile-ja.html"},{"nameIdentifier":"60363157","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://nrid.nii.ac.jp/ja/search/?qm=60363157"}]},{"creatorNames":[{"creatorName":"イタガキ, マミ","creatorNameLang":"ja"},{"creatorName":"イタガキ, マミ","creatorNameLang":"ja-Kana"},{"creatorName":"Itagaki, Mami","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Taha, Eman A.","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"オノ, キショウ","creatorNameLang":"ja"},{"creatorName":"オノ, キショウ","creatorNameLang":"ja-Kana"},{"creatorName":"Ono, Kisho","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"アオヤマ, エリコ","creatorNameLang":"ja"},{"creatorName":"アオヤマ, エリコ","creatorNameLang":"ja-Kana"},{"creatorName":"Aoyama, Eriko","creatorNameLang":"en"}]},{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"http://www.isni.org/isni/"}],"affiliationNames":[{"affiliationName":"","affiliationNameLang":"ja"}]}],"creatorNames":[{"creatorName":"岡村, 裕彦","creatorNameLang":"ja"},{"creatorName":"オカムラ, ヒロヒコ","creatorNameLang":"ja-Kana"},{"creatorName":"Okamura, Hirohiko","creatorNameLang":"en"}],"familyNames":[{"familyName":"岡村","familyNameLang":"ja"},{"familyName":"オカムラ","familyNameLang":"ja-Kana"},{"familyName":"Okamura","familyNameLang":"en"}],"givenNames":[{"givenName":"裕彦","givenNameLang":"ja"},{"givenName":"ヒロヒコ","givenNameLang":"ja-Kana"},{"givenName":"Hirohiko","givenNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"1256","nameIdentifierScheme":"WEKO"},{"nameIdentifier":"20380024","nameIdentifierScheme":"e-Rad","nameIdentifierURI":"https://nrid.nii.ac.jp/ja/search/?qm=20380024"}]},{"creatorNames":[{"creatorName":"コザキ, ケンイチ","creatorNameLang":"ja"},{"creatorName":"コザキ, ケンイチ","creatorNameLang":"ja-Kana"},{"creatorName":"Kozaki, Ken-ichi","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"Calderwood, Stuart K.","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"タキガワ, マサハル","creatorNameLang":"ja"},{"creatorName":"タキガワ, マサハル","creatorNameLang":"ja-Kana"},{"creatorName":"Takigawa, Masaharu","creatorNameLang":"en"}]},{"creatorNames":[{"creatorName":"オカモト, クニアキ","creatorNameLang":"ja"},{"creatorName":"オカモト, クニアキ","creatorNameLang":"ja-Kana"},{"creatorName":"Okamoto, Kuniaki","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":"2020-10-29"}],"displaytype":"detail","filename":"cancers_12_4_881.pdf","filesize":[{"value":"4.25 MB"}],"format":"application/pdf","licensetype":"license_0","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://tokushima-u.repo.nii.ac.jp/record/2007972/files/cancers_12_4_881.pdf"},"version_id":"7ac4d04b-5e59-4502-97a8-73a5c902e662"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"matrix metalloproteinase","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"moonlighting metalloproteinase (MMP)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"protein moonlighting","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"transcription factor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"extracellular vesicles","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"oncosome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"genome editing","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CRISPR","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"cellular communication network factor","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"CCN2/CTGF","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":"Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF) : CRISPR against Cancer","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF) : CRISPR against Cancer","subitem_title_language":"en"}]},"item_type_id":"40001","owner":"7","path":["1713853295607"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2020-10-29"},"publish_date":"2020-10-29","publish_status":"0","recid":"2007972","relation_version_is_last":true,"title":["Extracellular Vesicles Enriched with Moonlighting Metalloproteinase Are Highly Transmissive, Pro-Tumorigenic, and Trans-Activates Cellular Communication Network Factor (CCN2/CTGF) : CRISPR against Cancer"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2025-01-31T06:16:59.164108+00:00"}