{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T06:16:18Z","timestamp":1788243378042,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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 Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Peritoneal metastasis (PM) is a highly lethal pattern of progression in colorectal cancer (CRC), yet the specific molecular drivers and upstream regulatory mechanisms underlying this process remain incompletely understood. In the present study, public transcriptomic datasets from TCGA and GEO were integrated to identify PM\u2010associated genes in CRC, and prognostic relevance was evaluated using Kaplan\u2013Meier survival analysis and Cox regression. Stable knockdown and overexpression models were established to investigate the role of DKK1 in CRC cell migration, invasion and peritoneal dissemination using Transwell assays and a mouse peritoneal metastasis model. Multi\u2010cohort analysis identified 86 genes specifically upregulated in PM, among which DKK1 showed the most consistent overexpression and was significantly associated with poor prognosis in patients with CRC. Functionally, DKK1 knockdown significantly suppressed CRC cell migration, invasion and peritoneal metastatic colonization in\u00a0vivo, whereas DKK1 overexpression enhanced these malignant phenotypes. Mechanistically, DKK1 promoted metastasis in association with activation of the Wnt\/\u03b2\u2010catenin signalling programme and induction of epithelial\u2010mesenchymal transition. Upstream analysis demonstrated that the histone demethylase KDM6B was positively correlated with DKK1 expression and directly activated DKK1 transcription by binding to its promoter and reducing H3K27me3 enrichment. Rescue experiments further indicated that the pro\u2010metastatic and epithelial\u2010mesenchymal transition\u2010promoting effects of KDM6B were largely dependent on DKK1. Collectively, these findings identify DKK1 as a key driver of CRC PM and establish the KDM6B\u2010DKK1\u2010Wnt\/\u03b2\u2010catenin\u2010epithelial\u2010mesenchymal transition axis as a critical regulatory pathway in this process.<\/jats:p>","DOI":"10.1111\/jcmm.71326","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T04:53:53Z","timestamp":1787547233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Activation of the\n                    <scp>KDM6B<\/scp>\n                    \u2010\n                    <scp>DKK1<\/scp>\n                    Axis Promotes Colorectal Cancer Peritoneal Metastasis Through Wnt\/\u03b2\u2010Catenin\u2010Associated\n                    <scp>EMT<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"given":"Zhichao","family":"Zhai","sequence":"first","affiliation":[{"name":"Tianjin Nankai Hospital Tianjin Medical University  Tianjin China"},{"name":"Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair  Tianjin China"},{"name":"Institute of Integrative Medicine for Acute Abdominal Diseases  Tianjin China"},{"name":"Department of Gastrointestinal Surgery Peking University Shougang Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Peking University Shougang Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Peking University Shougang Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0818-1138","authenticated-orcid":false,"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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