{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T18:17:45Z","timestamp":1783707465760,"version":"3.55.0"},"reference-count":73,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"28","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:p>\n                    Plasticity, the capability of tumor cells to go through phenotypic transitions, promotes colorectal cancer (CRC) progression and treatment resistance. Although plasticity is evident in advanced CRCs, little is known about plasticity in early-stage tumors and tumor stem cells. Here, we demonstrate that a plastic cell state (PCS) is present already in polyps from patients with familial adenomatous polyposis and in mouse intestinal adenomas, in which PCS is associated with\n                    <jats:italic toggle=\"yes\">PROX1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    tumor stem cells. We furthermore analyzed progressive plasticity upon loss of the canonical wingless-related integration site (Wnt) effector\n                    <jats:italic toggle=\"yes\">Tcf7<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Lef1<\/jats:italic>\n                    in\n                    <jats:italic toggle=\"yes\">Apc<\/jats:italic>\n                    mutant mice. Deletion of either gene led to emergence of new plastic tumor cell populations, failure of leucine-rich repeat\u2013containing G protein-coupled receptor 5 (Lgr5) tumor stem cell differentiation into enterocyte-like cells, enhanced Myc pathway activation, and increased tumor cell proliferation and tumorigenesis. Together, we demonstrate that PCS is associated with early CRC development and identify multiple potentially druggable mechanisms activated during progressive tumor cell plasticity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb8564","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T17:58:37Z","timestamp":1783706317000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Progressive intestinal tumor cell plasticity, Myc activation, and loss of Lgr5\n                    <sup>+<\/sup>\n                    tumor stem cell lineage commitment upon Wnt depletion"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9591-2156","authenticated-orcid":true,"given":"Marika","family":"Lassila","sequence":"first","affiliation":[{"name":"Translational Cancer Medicine Program, Research Programs Unit, University of Helsinki, Helsinki 00014, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7248-1218","authenticated-orcid":true,"given":"Fatemeh","family":"Seyednasrollah","sequence":"additional","affiliation":[{"name":"Translational Cancer Medicine Program, Research Programs Unit, University of Helsinki, Helsinki 00014, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Bessone","sequence":"additional","affiliation":[{"name":"Translational Cancer Medicine Program, Research Programs Unit, University of Helsinki, Helsinki 00014, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2764-0433","authenticated-orcid":true,"given":"Maritta","family":"R\u00e4is\u00e4nen","sequence":"additional","affiliation":[{"name":"Medicum\/Department of Medical and Clinical Genetics, University of Helsinki, Helsinki 00014, Finland."},{"name":"Applied Tumor Genomics Research Program, Research 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