{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360002216804337280.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/ncomms7716"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/ncomms7716.pdf"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/ncomms7716"}},{"identifier":{"@type":"PMID","@value":"25828099"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene,<jats:italic>PDPK1</jats:italic>. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain<jats:italic>in vivo</jats:italic>. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380003444994342531","@type":"Researcher","foaf:name":[{"@value":"Naoomi Tominaga"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342528","@type":"Researcher","foaf:name":[{"@value":"Nobuyoshi Kosaka"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342535","@type":"Researcher","foaf:name":[{"@value":"Makiko Ono"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342530","@type":"Researcher","foaf:name":[{"@value":"Takeshi Katsuda"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342534","@type":"Researcher","foaf:name":[{"@value":"Yusuke Yoshioka"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342533","@type":"Researcher","foaf:name":[{"@value":"Kenji Tamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1380003444994342532","@type":"Researcher","foaf:name":[{"@value":"Jan 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Neoplasms"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20SCID","dc:title":"Mice, SCID"},{"@id":"https://cir.nii.ac.jp/all?q=Article","dc:title":"Article"},{"@id":"https://cir.nii.ac.jp/all?q=Actins","dc:title":"Actins"},{"@id":"https://cir.nii.ac.jp/all?q=3-Phosphoinositide-Dependent%20Protein%20Kinases","dc:title":"3-Phosphoinositide-Dependent Protein Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Expression%20Regulation,%20Neoplastic","dc:title":"Gene Expression Regulation, Neoplastic"},{"@id":"https://cir.nii.ac.jp/all?q=Extracellular%20Vesicles","dc:title":"Extracellular Vesicles"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=MicroRNAs","dc:title":"MicroRNAs"},{"@id":"https://cir.nii.ac.jp/all?q=Protein%20Transport","dc:title":"Protein Transport"},{"@id":"https://cir.nii.ac.jp/all?q=Actin%20Depolymerizing%20Factors","dc:title":"Actin Depolymerizing Factors"},{"@id":"https://cir.nii.ac.jp/all?q=Blood-Brain%20Barrier","dc:title":"Blood-Brain Barrier"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Line,%20Tumor","dc:title":"Cell Line, Tumor"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Phosphorylation","dc:title":"Phosphorylation"},{"@id":"https://cir.nii.ac.jp/all?q=Neoplasm%20Transplantation","dc:title":"Neoplasm Transplantation"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256773896064","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"14J05687"},{"@type":"JGN","@value":"JP14J05687"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14J05687/"}],"notation":[{"@language":"ja","@value":"がん由来エクソソームによる血液脳関門の破壊メカニズムの解明と診断治療への応用"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050287297274541952","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes."}]},{"@id":"https://cir.nii.ac.jp/crid/1050564288161039744","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Small RNAs detected in exosomes derived from the MH7A synovial fibroblast cell line with TNF-α 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