{"@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/1363670318324357504.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1038/s41467-018-08133-6"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-018-08133-6"}},{"identifier":{"@type":"URI","@value":"https://www.nature.com/articles/s41467-018-08133-6.pdf"}}],"dc:title":[{"@value":"ONECUT2 is a driver of neuroendocrine prostate cancer"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>Neuroendocrine prostate cancer (NEPC), a lethal form of the disease, is characterized by loss of androgen receptor (AR) signaling during neuroendocrine transdifferentiation, which results in resistance to AR-targeted therapy. Clinically, genomically and epigenetically, NEPC resembles other types of poorly differentiated neuroendocrine tumors (NETs). Through pan-NET analyses, we identified ONECUT2 as a candidate master transcriptional regulator of poorly differentiated NETs. ONECUT2 ectopic expression in prostate adenocarcinoma synergizes with hypoxia to suppress androgen signaling and induce neuroendocrine plasticity. ONEUCT2 drives tumor aggressiveness in NEPC, partially through regulating hypoxia signaling and tumor hypoxia. Specifically, ONECUT2 activates SMAD3, which regulates hypoxia signaling through modulating HIF1α chromatin-binding, leading NEPC to exhibit higher degrees of hypoxia compared to prostate adenocarcinomas. Treatment with hypoxia-activated prodrug TH-302 potently reduces NEPC tumor growth. Collectively, these results highlight the synergy between ONECUT2 and hypoxia in driving NEPC, and emphasize the potential of hypoxia-directed therapy for NEPC patients.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670318324357377","@type":"Researcher","foaf:name":[{"@value":"Haiyang Guo"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357395","@type":"Researcher","foaf:name":[{"@value":"Xinpei Ci"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357392","@type":"Researcher","foaf:name":[{"@value":"Musaddeque Ahmed"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357509","@type":"Researcher","foaf:name":[{"@value":"Junjie Tony Hua"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357389","@type":"Researcher","foaf:name":[{"@value":"Fraser Soares"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357381","@type":"Researcher","foaf:name":[{"@value":"Dong Lin"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357391","@type":"Researcher","foaf:name":[{"@value":"Loredana Puca"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357251","@type":"Researcher","foaf:name":[{"@value":"Aram Vosoughi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357505","@type":"Researcher","foaf:name":[{"@value":"Hui Xue"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357380","@type":"Researcher","foaf:name":[{"@value":"Estelle Li"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357383","@type":"Researcher","foaf:name":[{"@value":"Peiran Su"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357385","@type":"Researcher","foaf:name":[{"@value":"Sujun Chen"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357397","@type":"Researcher","foaf:name":[{"@value":"Tran Nguyen"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357510","@type":"Researcher","foaf:name":[{"@value":"Yi Liang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357376","@type":"Researcher","foaf:name":[{"@value":"Yuzhe Zhang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357384","@type":"Researcher","foaf:name":[{"@value":"Xin Xu"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357382","@type":"Researcher","foaf:name":[{"@value":"Jing Xu"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357512","@type":"Researcher","foaf:name":[{"@value":"Anjali V. Sheahan"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357387","@type":"Researcher","foaf:name":[{"@value":"Wail Ba-Alawi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357390","@type":"Researcher","foaf:name":[{"@value":"Si Zhang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357394","@type":"Researcher","foaf:name":[{"@value":"Osman Mahamud"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357398","@type":"Researcher","foaf:name":[{"@value":"Ravi N. Vellanki"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357506","@type":"Researcher","foaf:name":[{"@value":"Martin Gleave"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357504","@type":"Researcher","foaf:name":[{"@value":"Robert G. Bristow"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357399","@type":"Researcher","foaf:name":[{"@value":"Benjamin Haibe-Kains"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357248","@type":"Researcher","foaf:name":[{"@value":"John T. Poirier"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357388","@type":"Researcher","foaf:name":[{"@value":"Charles M. Rudin"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357252","@type":"Researcher","foaf:name":[{"@value":"Ming-Sound Tsao"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357507","@type":"Researcher","foaf:name":[{"@value":"Bradly G. Wouters"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357379","@type":"Researcher","foaf:name":[{"@value":"Ladan Fazli"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357378","@type":"Researcher","foaf:name":[{"@value":"Felix Y. Feng"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357254","@type":"Researcher","foaf:name":[{"@value":"Leigh Ellis"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357393","@type":"Researcher","foaf:name":[{"@value":"Theo van der Kwast"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357396","@type":"Researcher","foaf:name":[{"@value":"Alejandro Berlin"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357249","@type":"Researcher","foaf:name":[{"@value":"Marianne Koritzinsky"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357253","@type":"Researcher","foaf:name":[{"@value":"Paul C. Boutros"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357386","@type":"Researcher","foaf:name":[{"@value":"Amina Zoubeidi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357511","@type":"Researcher","foaf:name":[{"@value":"Himisha Beltran"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357250","@type":"Researcher","foaf:name":[{"@value":"Yuzhuo Wang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318324357508","@type":"Researcher","foaf:name":[{"@value":"Housheng Hansen He"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20411723"}],"prism:publicationName":[{"@value":"Nature Communications"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2019-01-17","prism:volume":"10","prism:number":"1","prism:startingPage":"278"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://www.nature.com/articles/s41467-018-08133-6"},{"@id":"https://www.nature.com/articles/s41467-018-08133-6.pdf"}],"createdAt":"2019-01-11","modifiedAt":"2022-12-16","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360290617683584896","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360298757190713984","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Targeting phase separation on enhancers induced by transcription factor complex formations as a new strategy for treating drug-resistant cancers"}]},{"@id":"https://cir.nii.ac.jp/crid/1360302864791009024","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Decoding the basis of histological variation in human cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360576118763763712","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380582794496","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"PROX1 is a regulator of neuroendocrine-related gene expression in lung carcinoid"}]},{"@id":"https://cir.nii.ac.jp/crid/1361694366532069504","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Dedifferentiation of neuroendocrine carcinoma of the uterine cervix in hypoxia"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1038/s41467-018-08133-6"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2020.01.024_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"},{"@type":"CROSSREF","@value":"10.1016/j.celrep.2020.108585_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"},{"@type":"CROSSREF","@value":"10.3389/fonc.2022.1024600_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"},{"@type":"CROSSREF","@value":"10.1038/s41568-023-00648-5_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"},{"@type":"CROSSREF","@value":"10.1038/s41467-021-23974-4_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"},{"@type":"CROSSREF","@value":"10.1007/s13577-024-01109-3_references_DOI_YhkvsdePoR2dRws4uAnaX0en118"}]}