{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:47:37Z","timestamp":1782110857250,"version":"3.54.5"},"reference-count":66,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The role of the transcription factor\n                    <jats:italic>Wt1<\/jats:italic>\n                    in prostate cancer (PCa) remains unclear. This study utilized public scRNA\u2010seq datasets and TCGA data to investigate how\n                    <jats:italic>Wt1<\/jats:italic>\n                    regulates the transition from normal fibroblasts (NFs) to cancer\u2010associated fibroblasts (CAFs) by activating the\n                    <jats:italic>Spon2<\/jats:italic>\n                    axis. The results identified seven distinct cell types in PCa tissues through scRNA\u2010seq annotation, revealing the heterogeneity of CAFs in PCa. Through screening,\n                    <jats:italic>Spon2<\/jats:italic>\n                    was identified as a key gene involved in the transition from NFs to CAFs. Further upstream transcription factor prediction identified\n                    <jats:italic>Wt1<\/jats:italic>\n                    as a regulator of\n                    <jats:italic>Spon2<\/jats:italic>\n                    , and in vitro mechanistic experiments confirmed that\n                    <jats:italic>Wt1<\/jats:italic>\n                    transcriptionally activates\n                    <jats:italic>Spon2<\/jats:italic>\n                    , thereby promoting the conversion of NFs into CAFs. In vitro functional assays demonstrated that knocking down\n                    <jats:italic>Wt1<\/jats:italic>\n                    in CAFs inhibited\n                    <jats:italic>Spon2<\/jats:italic>\n                    expression, leading to reduced PCa cell metabolism, suppression of proliferation, migration, and invasion, while promoting apoptosis. Moreover, in vivo animal experiments confirmed that activation of the\n                    <jats:italic>Wt1\/Spon2<\/jats:italic>\n                    signaling axis promotes the conversion of NFs to CAFs, thereby enhancing tumorigenesis in PCa cells. In summary,\n                    <jats:italic>Wt1<\/jats:italic>\n                    promotes the transition of NFs into CAFs by activating\n                    <jats:italic>Spon2<\/jats:italic>\n                    expression, which enhances PCa cell metabolism, promotes proliferation, migration, and invasion, and inhibits apoptosis, ultimately facilitating PCa tumor growth in vivo.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70800","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T09:06:33Z","timestamp":1779095193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Role of\n                    <i>Wt1\/Spon2<\/i>\n                    Axis in Prostate Cancer Progression and Fibroblast Dynamics"],"prefix":"10.1002","volume":"40","author":[{"given":"Dun","family":"Xue","sequence":"first","affiliation":[{"name":"Department of Medical The First Hospital of Changsha  Changsha P. 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