{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T03:49:44Z","timestamp":1794368984171,"version":"4.9.0"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Epithelial\u2010to\u2010mesenchymal transition (EMT) is an early event during tumor metastasis. Here, the relevance of EMT in liver carcinogenesis and metastasis is sought to be determined in a murine mixed typical intrahepatic cholangiocarcinoma (iCCA)\/sarcomatoid iCCA liver tumor model using CRISPR\/Cas9\u2010based gene deletion of p19 (\n                    <jats:italic>sgP19)<\/jats:italic>\n                    in combination with transposon\u2010based expression of the activated form of pCaggs\u2010kRAS\n                    <jats:sup>G12D<\/jats:sup>\n                    (\n                    <jats:italic>kRAS)<\/jats:italic>\n                    in the mouse liver (\n                    <jats:italic>sgP19\/kRAS<\/jats:italic>\n                    mixed model). It discovered that metastasis in the lymph node, lung, or kidney occurred in the\n                    <jats:italic>sgP19\/kRAS<\/jats:italic>\n                    mixed model. Both typical iCCA tumor cells with epithelial features and sarcomatoid tumor cells with mesenchymal features could be detected in this model. Lineage tracing technology is applied to confirm the metastasis induced in the\n                    <jats:italic>sgP19\/kRAS<\/jats:italic>\n                    model. Subsequently, the gain of expression of mesenchymal marker vimentin in tumor cells revealed the induction of EMT in the\n                    <jats:italic>sgP19\/kRAS<\/jats:italic>\n                    model, and it is induced by activating the TGF\u03b2\/ZEB1 signaling pathway. Altogether, the study suggests that TGF\u03b2\/ZEB1 mediates the induction of EMT in iCCA, while targeting EMT failed to inhibit iCCA development or tumor metastasis, disputing the claims that EMT is a major molecular event leading to tumor metastasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202514198","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T03:30:25Z","timestamp":1765164625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncoupling Metastasis and Epithelial\u2010to\u2010Mesenchymal Transition in sgP19\/kRAS\u2010Driven Spontaneous Metastatic Liver Tumor Model"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingwen","family":"Wang","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Laboratory for Clinical Medicine Capital Medical University  Beijing 100069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijing","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Laboratory for Clinical Medicine Capital Medical University  Beijing 100069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing Jiangsu Province 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing Jiangsu Province 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Laboratory for Clinical Medicine Capital Medical University  Beijing 100069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Biology Program University of Hawai'i Cancer Center University of Hawai'i  Honolulu Hawaii HI 96813 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital of Xi'an Jiaotong University  Xian Shaanxi Province 710004 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Superville","sequence":"additional","affiliation":[{"name":"Department of Cell and Tissue Biology UCSF  San Francisco CA CA 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Reeves","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute University of Utah  Salt Lake City UT UT 84112 USA"},{"name":"Department of Pathology University of Utah  Salt Lake City UT Utah 84112 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Evert","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of Regensburg  93053 Regensburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego F.","family":"Calvisi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery, and Pharmacy University of Sassari  Sassari 07100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-0164","authenticated-orcid":false,"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Cancer Biology Program University of Hawai'i Cancer Center University of Hawai'i  Honolulu Hawaii HI 96813 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhua","family":"Song","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Laboratory for Clinical Medicine Capital Medical University  Beijing 100069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10010104"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.157"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0310-z"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-019-06142-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8889571"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13040791"},{"key":"e_1_2_9_8_1","first-page":"5563","volume":"79","author":"Xu M.","year":"2019","journal-title":"Murine Hepatocell. 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