{"@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/1360004236367367808.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1158/0008-5472.can-18-1749"}},{"identifier":{"@type":"URI","@value":"https://aacrjournals.org/cancerres/article-pdf/78/21/6107/2773130/6107.pdf"}},{"identifier":{"@type":"PMID","@value":"30181180"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"p63-Dependent Dickkopf3 Expression Promotes Esophageal Cancer Cell Proliferation via CKAP4"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:p>Dickkopf3 (DKK3) is a secretory protein that belongs to the DKK family, but exhibits structural divergence from other family members, and its corresponding receptors remain to be identified. Although DKK3 has been shown to have oncogenic functions in certain cancer types, the underlying mechanism by which DKK3 promotes tumorigenesis remains to be clarified. We show here that DKK3 stimulates esophageal cancer cell proliferation via cytoskeleton-associated protein 4 (CKAP4), which acts as a receptor for DKK3. DKK3 was expressed in approximately 50% of tumor lesions of esophageal squamous cell carcinoma (ESCC) cases; simultaneous expression of DKK3 and CKAP4 was associated with poor prognosis. Anti-CKAP4 antibody inhibited both binding of DKK3 to CKAP4 and xenograft tumor formation induced by ESCC cells. p63, a p53-related transcriptional factor frequently amplified in ESCC, bound to the upstream region of the DKK3 gene. Knockdown of p63 decreased DKK3 expression in ESCC cells, and reexpression of DKK3 partially rescued cell proliferation in p63-depleted ESCC cells. Expression of ΔNp63α and DKK3 increased the size of tumor-like esophageal organoids, and anti-CKAP4 antibody inhibited growth of esophageal organoids. Taken together, these results suggest that the DKK3-CKAP4 axis might serve as a novel molecular target for ESCC.</jats:p>\n                  <jats:p>Significance: In esophageal cancer, findings identify DKK3 as a poor prognostic indicator and demonstrate CKAP4 inhibition as an effective therapeutic strategy. Cancer Res; 78(21); 6107–20. ©2018 AACR.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004236367367684","@type":"Researcher","foaf:name":[{"@value":"Chihiro Kajiwara"}],"jpcoar:affiliationName":[{"@value":"1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1380004236367367682","@type":"Researcher","foaf:name":[{"@value":"Katsumi Fumoto"}],"jpcoar:affiliationName":[{"@value":"1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1380004236367367686","@type":"Researcher","foaf:name":[{"@value":"Hirokazu Kimura"}],"jpcoar:affiliationName":[{"@value":"1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1380004236367367808","@type":"Researcher","foaf:name":[{"@value":"Satoshi Nojima"}],"jpcoar:affiliationName":[{"@value":"2Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1380004236367367689","@type":"Researcher","foaf:name":[{"@value":"Keita Asano"}],"jpcoar:affiliationName":[{"@value":"1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan."}]},{"@id":"https://cir.nii.ac.jp/crid/1380004236367367680","@type":"Researcher","foaf:name":[{"@value":"Kazuki Odagiri"}],"jpcoar:affiliationName":[{"@value":"3Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, 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Kikuchi"}],"jpcoar:affiliationName":[{"@value":"1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00085472"},{"@type":"EISSN","@value":"15387445"}],"prism:publicationName":[{"@value":"Cancer Research"}],"dc:publisher":[{"@value":"American Association for Cancer Research (AACR)"}],"prism:publicationDate":"2018-11-01","prism:volume":"78","prism:number":"21","prism:startingPage":"6107","prism:endingPage":"6120"},"reviewed":"false","url":[{"@id":"https://aacrjournals.org/cancerres/article-pdf/78/21/6107/2773130/6107.pdf"}],"createdAt":"2018-09-04","modifiedAt":"2022-06-17","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Adult","dc:title":"Adult"},{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Esophageal%20Neoplasms","dc:title":"Esophageal Neoplasms"},{"@id":"https://cir.nii.ac.jp/all?q=Carcinogenesis","dc:title":"Carcinogenesis"},{"@id":"https://cir.nii.ac.jp/all?q=Madin%20Darby%20Canine%20Kidney%20Cells","dc:title":"Madin Darby Canine Kidney Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Dogs","dc:title":"Dogs"},{"@id":"https://cir.nii.ac.jp/all?q=Genes,%20Reporter","dc:title":"Genes, Reporter"},{"@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=Adaptor%20Proteins,%20Signal%20Transducing","dc:title":"Adaptor Proteins, Signal Transducing"},{"@id":"https://cir.nii.ac.jp/all?q=Aged","dc:title":"Aged"},{"@id":"https://cir.nii.ac.jp/all?q=Cell%20Proliferation","dc:title":"Cell Proliferation"},{"@id":"https://cir.nii.ac.jp/all?q=Aged,%2080%20and%20over","dc:title":"Aged, 80 and over"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Knockout","dc:title":"Mice, Knockout"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20BALB%20C","dc:title":"Mice, Inbred BALB C"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Suppressor%20Proteins","dc:title":"Tumor Suppressor Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Membrane%20Proteins","dc:title":"Membrane Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Hep%20G2%20Cells","dc:title":"Hep G2 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Middle%20Aged","dc:title":"Middle Aged"},{"@id":"https://cir.nii.ac.jp/all?q=HCT116%20Cells","dc:title":"HCT116 Cells"},{"@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=HEK293%20Cells","dc:title":"HEK293 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=A549%20Cells","dc:title":"A549 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Intercellular%20Signaling%20Peptides%20and%20Proteins","dc:title":"Intercellular Signaling Peptides and Proteins"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Esophageal%20Squamous%20Cell%20Carcinoma","dc:title":"Esophageal Squamous Cell Carcinoma"},{"@id":"https://cir.nii.ac.jp/all?q=Caco-2%20Cells","dc:title":"Caco-2 Cells"},{"@id":"https://cir.nii.ac.jp/all?q=Chemokines","dc:title":"Chemokines"},{"@id":"https://cir.nii.ac.jp/all?q=Neoplasm%20Transplantation","dc:title":"Neoplasm Transplantation"},{"@id":"https://cir.nii.ac.jp/all?q=Transcription%20Factors","dc:title":"Transcription Factors"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781902512128","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16H06276"},{"@type":"JGN","@value":"JP16H06276"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16H06276/"},{"@type":"KAKEN","@value":"16H06276"}],"notation":[{"@language":"ja","@value":"先端モデル動物支援プラットフォーム"},{"@language":"en","@value":"Advanced Animal Model 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mechanisms that cause cancers due to the abnormality of Wnt signal network"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050012810923558656","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Establishment of anti-DKK3 peptide for the cancer control in head and neck squamous cell carcinoma (HNSCC)"}]},{"@id":"https://cir.nii.ac.jp/crid/1050282810815032448","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Recent Advances from Basic and Clinical Studies of Esophageal Squamous Cell Carcinoma"}]},{"@id":"https://cir.nii.ac.jp/crid/1050565162867595264","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"DNA methylation status of REIC/Dkk-3 gene in human 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