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CDC7 is a kinase that regulates DNA replication and is found elevated during neuroendocrine transdifferentiation in lung and prostate cancer. In this study, we demonstrate that CDC7 is highly expressed in treatment-resistant prostate cancer, with even higher levels observed in treatment-resistant prostate cancer with neuroendocrine phenotype (NEPC). We further identify CDC7 as a critical regulator of prostate tumorigenesis. Downregulation of CDC7 significantly reduces prostate cancer cells growth and invasion\n                    <jats:italic>in vitro<\/jats:italic>\n                    and silencing CDC7 suppresses prostate tumor growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Furthermore, we demonstrate that the inhibition of CDC7 using TAK-931, a selective CDC7 inhibitor, significantly reduces the proliferation, migration, and invasion of aggressive prostate cancer cells. TAK-931 treated prostate cancer cells exhibit an abnormal cell cycle profile, suggesting that CDC7 inhibition induces replication stress and promotes apoptosis. Collectively, our findings demonstrate that CDC7 is a regulator of tumor progression in prostate cancer and represents new therapeutic target in advanced prostate cancer.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-29574-2","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T10:53:26Z","timestamp":1766055206000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CDC7 is a targetable regulator of advanced prostate cancer"],"prefix":"10.1038","volume":"16","author":[{"given":"Alifiani B.","family":"Hartono","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"HyeonJi","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sidharth","family":"Paparaju","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James D.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Corey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya","family":"Stoyanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"29574_CR1","doi-asserted-by":"crossref","unstructured":"Siegel, R. 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Methods Protoc."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29574-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29574-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29574-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:02:36Z","timestamp":1768006956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29574-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["29574"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-29574-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]},"assertion":[{"value":"3 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest regarding this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All experimental procedures using mice were performed in agreement with protocols approved by Institutional Animal Care and Use Committee (IACUC) of University of California, Los Angeles (protocol no. ARC-2022\u2013122). All animal experiments followed National Institutes of Health guidelines for animal welfare and adhered to the ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"For tumor implantation, cancer cells (1\u2009\u00d7\u200910\n                      6\n                      ) were resuspended in 50 \u00b5L of PBS and mixed with 50\u00a0\u00b5l of 100% Matrigel and implanted subcutaneously in both flanks of male NOD\/SCID\/IL-2R\u03b3null (NSG) mice. The tumor length (L), width (W), and height (H) were measured every three days, and tumor volumes were calculated (\u00bd LxWxH). At end point, mice were euthanized by administering CO2 in a compressed commercial cylinder with a flow meter rate of 30\u201370% of the chamber volume\/minute for at least 5\u00a0min. A cervical dislocation was used as a secondary euthanasia method. Tumors were collected, weighed, and processed for downstream analyses by overnight fixation with 10% buffered formalin followed by tissue processing and embedding in paraffin (FFPE).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animals and in vivo tumor growth"}}],"article-number":"308"}}