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Highly proliferative regions with embryonal histology show high expression of Wnt target genes, the embryonic biliary transcription factor\n                    <jats:italic>SOX4<\/jats:italic>\n                    , and striking focal expression of the growth factor\n                    <jats:italic>FGF19<\/jats:italic>\n                    . In patient-derived tumoroids with constitutive Wnt activation, FGF19 is a required growth signal for FGF19-negative cells. Indeed, some tumoroids contain subsets of cells that endogenously express\n                    <jats:italic>FGF19<\/jats:italic>\n                    , downstream of Wnt\/\u03b2-catenin and SOX4. Thus, the embryonic biliary lineage program cooperates with stabilized nuclear \u03b2-catenin, inducing FGF19 as a paracrine growth signal that promotes tumor cell proliferation, together with active Wnt signaling. In this pediatric cancer presumed to originate from a multipotent hepatobiliary progenitor, lineage-driven heterogeneity results in a functional growth advantage, a non-genetic mechanism whereby developmental lineage programs influence tumor evolution.\n                  <\/jats:p>","DOI":"10.1038\/s41467-024-53802-4","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T05:08:15Z","timestamp":1732079295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-0002","authenticated-orcid":false,"given":"Peng V.","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Fish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florette K.","family":"Hazard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujay","family":"Vennam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Walton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay","family":"Wagh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Coller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Przybyl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Morri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-5420","authenticated-orcid":false,"given":"Norma","family":"Neff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7082-3748","authenticated-orcid":false,"given":"Roel","family":"Nusse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"53802_CR1","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1126\/science.959840","volume":"194","author":"PC Nowell","year":"1976","unstructured":"Nowell, P. 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