{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:20:49Z","timestamp":1791368449343,"version":"4.3.1"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"8","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32270821"],"award-info":[{"award-number":["32270821"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The National Natural Science Foundation of Zhejiang","award":["LY24C050001"],"award-info":[{"award-number":["LY24C050001"]}]},{"name":"The National Natural Science Foundation of Zhejiang","award":["LTGY24H160005"],"award-info":[{"award-number":["LTGY24H160005"]}]},{"name":"The Youth Science and Technology Innovation Leader of Ningbo","award":["2023QL052"],"award-info":[{"award-number":["2023QL052"]}]},{"DOI":"10.13039\/501100020738","name":"The K.C. Wong Magna Fund in Ningbo University","doi-asserted-by":"crossref","award":["Not Applicable"],"award-info":[{"award-number":["Not Applicable"]}],"id":[{"id":"10.13039\/501100020738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Ningbo Clinical Research Center for Urological Disease","award":["2019A21001"],"award-info":[{"award-number":["2019A21001"]}]},{"name":"The Ningbo Top Medical and Health Research Program","award":["2022020203"],"award-info":[{"award-number":["2022020203"]}]},{"name":"Zhejiang Engineering Research Center of Innovative technologies and diagnostic and therapeutic equipment for urinary system diseases","award":["Not Applicable"],"award-info":[{"award-number":["Not Applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:p>\n                    It is well documented that impaired DNA damage repair (DDR) induces genomic instability that can efficiently increase the sensitivity of prostate cancer (PCa) cells to PARP inhibitors; however, the underlying mechanism remains elusive. Here, we found profound genomic instability in PCa cells with\n                    <jats:italic>SPOP<\/jats:italic>\n                    gene mutations and confirmed the sensitivity of\n                    <jats:italic>SPOP<\/jats:italic>\n                    -mutated PCa cells to olaparib-induced apoptosis. Mechanistically, we identified olaparib-induced CK2-mediated phosphorylation of PIAS1-S468, which in turn mediated SUMOylation of SPOP, thus promoting its E3 ligase activity in the DDR. Moreover, an abnormal CK2\/PIAS1\/SPOP axis due to\n                    <jats:italic>SPOP<\/jats:italic>\n                    mutations or defects in CK2-mediated phosphorylation of PIAS1, as well as SPOP inhibitor treatment, led to impaired DDR, thus increasing olaparib-induced apoptosis of PCa cells and enhancing olaparib sensitivity in animal models and patient-derived organoids. This suggested that disruption of the CK2\/PIAS1\/SPOP signaling axis could serve as an indicator for targeted therapy of PCa using a PARP inhibitor.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.186871","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T14:00:44Z","timestamp":1745244044000},"source":"Crossref","is-referenced-by-count":9,"title":["SPOP mutations increase PARP inhibitor sensitivity via CK2\/PIAS1\/SPOP axis in prostate cancer"],"prefix":"10.1172","volume":"10","author":[{"given":"Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangpei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, The Affiliated People\u2019s Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjie","family":"You","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yadong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zejun","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China."},{"name":"Department of Biochemistry and Molecular Biology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,4,22]]},"reference":[{"issue":"10437","key":"B1","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/S0140-6736(24)00651-2","article-title":"The Lancet Commission on prostate cancer: planning for the surge in cases","volume":"403","author":"James","year":"2024","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.01.011"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00382-0"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3577"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2023.11.014"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abd9208"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab489"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-2801"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37499-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1439"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24269"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00381-7"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26049-6"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-05310-z"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2022.02.013"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2021.11.006"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.05.006"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04957-4"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.3366"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-1025-0_12"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-020-00566-w"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32804"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.02.020"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.21.3393"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.01.013"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00161"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2023.09.003"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgu022"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-1010"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01228-0"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01523"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2024.04.011"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.16996"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk8908"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-024-00929-7"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.04.012"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24481"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1716349115"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021836118"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32920-x"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2019.11.001"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.333"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.054"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30568-1"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112006"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/186871\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:05:13Z","timestamp":1779134713000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/186871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,22]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,3,4]]},"published-print":{"date-parts":[[2025,4,22]]}},"alternative-id":["10.1172\/jci.insight.186871"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.186871","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,22]]},"article-number":"e186871"}}