{"@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/1360007216730179072.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1136/gutjnl-2018-317645"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1136/gutjnl-2018-317645"}},{"identifier":{"@type":"PMID","@value":"31085554"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, can confer aggressive properties to cancer cells by secreting multiple factors. Their phenotypes are stably maintained, but the mechanisms are not fully understood. We aimed to show the critical role of epigenetic changes in CAFs in maintaining their tumour-promoting capacity and to show the validity of the epigenomic approach in identifying therapeutic targets from CAFs to starve cancer cells.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Design</jats:title>\n                    <jats:p>Twelve pairs of primary gastric CAFs and their corresponding non-CAFs (NCAFs) were established from surgical specimens. Genome-wide DNA methylation and H3K27me3 analyses were conducted by BeadArray 450K and ChIP-on-Chip, respectively. Functions of potential a therapeutic target were analysed by inhibiting it, and prognostic impact was assessed in a database.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>\n                      CAFs had diverse and distinct DNA methylation and H3K27me3 patterns compared with NCAFs. Loss of H3K27me3, but not DNA methylation, in CAFs was enriched for genes involved in stem cell niche, cell growth, tissue development and stromal–epithelial interactions, such as\n                      <jats:italic>WNT5A</jats:italic>\n                      ,\n                      <jats:italic>GREM1</jats:italic>\n                      ,\n                      <jats:italic>NOG</jats:italic>\n                      and\n                      <jats:italic>IGF2</jats:italic>\n                      . Among these, we revealed that WNT5A, which had been considered to be derived from cancer cells, was highly expressed in cancer stromal fibroblasts, and was associated with poor prognosis. Inhibition of secreted WNT5A from CAFs suppressed cancer cell growth and migration.\n                    </jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions</jats:title>\n                    <jats:p>H3K27me3 plays a crucial role in defining tumour-promoting capacities of CAFs, and multiple stem cell niche factors were secreted from CAFs due to loss of H3K27me3. The validity of the epigenetic approach to uncover therapeutic targets for cancer-starving therapy was demonstrated.</jats:p>\n                  </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1420864424387360384","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30738703"},{"@type":"NRID","@value":"1000030738703"},{"@type":"NRID","@value":"9000006315001"},{"@type":"NRID","@value":"9000006216007"},{"@type":"NRID","@value":"9000310340474"},{"@type":"NRID","@value":"9000004984226"},{"@type":"NRID","@value":"9000025045559"},{"@type":"NRID","@value":"9000004408510"},{"@type":"NRID","@value":"9000002442178"},{"@type":"NRID","@value":"9000324988434"},{"@type":"NRID","@value":"9000347205412"},{"@type":"NRID","@value":"9000004984224"},{"@type":"NRID","@value":"9000356648393"},{"@type":"NRID","@value":"9000258277207"}],"foaf:name":[{"@value":"Masahiro Maeda"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"},{"@value":"Department of Gastrointestinal Surgery, Faculty of Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178952","@type":"Researcher","foaf:name":[{"@value":"Hideyuki Takeshima"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179087","@type":"Researcher","foaf:name":[{"@value":"Naoko Iida"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179075","@type":"Researcher","foaf:name":[{"@value":"Naoko Hattori"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179076","@type":"Researcher","foaf:name":[{"@value":"Satoshi Yamashita"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179080","@type":"Researcher","foaf:name":[{"@value":"Hiroshi Moro"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179077","@type":"Researcher","foaf:name":[{"@value":"Yoshimi Yasukawa"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179079","@type":"Researcher","foaf:name":[{"@value":"Kazuhiro Nishiyama"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178946","@type":"Researcher","foaf:name":[{"@value":"Taiki Hashimoto"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179082","@type":"Researcher","foaf:name":[{"@value":"Shigeki Sekine"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178957","@type":"Researcher","foaf:name":[{"@value":"Genichiro Ishii"}],"jpcoar:affiliationName":[{"@value":"Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, Chiba, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179078","@type":"Researcher","foaf:name":[{"@value":"Atsushi Ochiai"}],"jpcoar:affiliationName":[{"@value":"Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178948","@type":"Researcher","foaf:name":[{"@value":"Takeo Fukagawa"}],"jpcoar:affiliationName":[{"@value":"Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730179085","@type":"Researcher","foaf:name":[{"@value":"Hitoshi Katai"}],"jpcoar:affiliationName":[{"@value":"Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178949","@type":"Researcher","foaf:name":[{"@value":"Yoshiharu Sakai"}],"jpcoar:affiliationName":[{"@value":"Department of Gastrointestinal Surgery, Faculty of Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380007216730178953","@type":"Researcher","foaf:name":[{"@value":"Toshikazu Ushijima"}],"jpcoar:affiliationName":[{"@value":"Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00175749"},{"@type":"EISSN","@value":"14683288"}],"prism:publicationName":[{"@value":"Gut"}],"dc:publisher":[{"@value":"BMJ"}],"prism:publicationDate":"2019-05-13","prism:volume":"69","prism:number":"2","prism:startingPage":"243","prism:endingPage":"251"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","url":[{"@id":"https://syndication.highwire.org/content/doi/10.1136/gutjnl-2018-317645"}],"createdAt":"2019-05-13","modifiedAt":"2025-11-21","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Epigenomics","dc:title":"Epigenomics"},{"@id":"https://cir.nii.ac.jp/all?q=Jumonji%20Domain-Containing%20Histone%20Demethylases","dc:title":"Jumonji Domain-Containing Histone Demethylases"},{"@id":"https://cir.nii.ac.jp/all?q=DNA,%20Neoplasm","dc:title":"DNA, Neoplasm"},{"@id":"https://cir.nii.ac.jp/all?q=DNA%20Methylation","dc:title":"DNA Methylation"},{"@id":"https://cir.nii.ac.jp/all?q=Gene%20Ontology","dc:title":"Gene Ontology"},{"@id":"https://cir.nii.ac.jp/all?q=Cancer-Associated%20Fibroblasts","dc:title":"Cancer-Associated Fibroblasts"},{"@id":"https://cir.nii.ac.jp/all?q=Stomach%20Neoplasms","dc:title":"Stomach Neoplasms"},{"@id":"https://cir.nii.ac.jp/all?q=Culture%20Media,%20Conditioned","dc:title":"Culture Media, Conditioned"},{"@id":"https://cir.nii.ac.jp/all?q=Mutation","dc:title":"Mutation"},{"@id":"https://cir.nii.ac.jp/all?q=Tumor%20Cells,%20Cultured","dc:title":"Tumor Cells, Cultured"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Stem%20Cell%20Niche","dc:title":"Stem Cell Niche"},{"@id":"https://cir.nii.ac.jp/all?q=Genome-Wide%20Association%20Study","dc:title":"Genome-Wide Association Study"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000781926313984","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"16K19959"},{"@type":"JGN","@value":"JP16K19959"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16K19959/"}],"notation":[{"@language":"ja","@value":"胃がん関連線維芽細胞のエピジェネティック特性の解明"},{"@language":"en","@value":"Identification of epigenetic characteristics of Cancer-associated fibroblasts"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050845760669907200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation."}]},{"@id":"https://cir.nii.ac.jp/crid/1360002217765321856","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"WNT Pathway Gene 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