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@ARTICLE{Wouters:300284,
      author       = {V. M. Wouters and R. F. C. P. A. Helderman and K. Cameron
                      and S. R. van der Hooff and A. Torang and S. van den Bergh
                      and R. Jackstadt$^*$ and O. J. Sansom and S. M. van Neerven
                      and J. P. Medema},
      title        = {{CDX}2 downregulation regulates intrinsic {WNT} pathway
                      activation, dictating metastasis in {APC} and {CTNNB}1
                      wildtype colorectal cancer.},
      journal      = {Oncogene},
      volume       = {44},
      number       = {25},
      issn         = {0950-9232},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00737},
      pages        = {2091-2102},
      year         = {2025},
      note         = {2025 Jul;44(25):2091-2102},
      abstract     = {Colorectal cancer (CRC) can be divided into 4 subtypes of
                      which consensus molecular subtype 4 (CMS4) is associated
                      with metastasis and poor survival. Previously, we reported
                      that the KPN mouse model resembles human CMS4. Strikingly,
                      although tumor formation in this model is slow and limited,
                      effective metastasis is observed. To understand this
                      aggressive behavior, we compared two distinct in vitro KPN
                      models, organoids and tumoroids. The organoid model only
                      carries the original mutations, while the tumoroids are
                      derived from in vivo grown tumors that underwent selection
                      during development. Here, we reveal that tumoroids harbor
                      endogenous WNT pathway activity, which can be driven by
                      tankyrase activity and Cdx2 downregulation. Importantly, WNT
                      pathway activation was heterogeneous in nature, subject to
                      regulation and allowed for a mixture of WNT-driven and
                      YAP-driven cells within tumoroids. This unique type of WNT
                      pathway activation is not crucial for colonic tumor growth,
                      but results in metastatic spreading. Intriguingly, these
                      findings reflect a specific subset of aggressive human CMS4
                      cancers that display low CDX2 expression and lack of
                      classical WNT pathway mutations, while having a higher
                      tendency to metastasize. Together, these data propose a
                      novel mechanism for WNT pathway activation that drives
                      metastasis formation in aggressive CRC.},
      cin          = {A013},
      ddc          = {610},
      cid          = {I:(DE-He78)A013-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40189705},
      doi          = {10.1038/s41388-025-03365-5},
      url          = {https://inrepo02.dkfz.de/record/300284},
}