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@ARTICLE{HoaHo:292488,
      author       = {K. Hoa Ho$^*$ and M. Trapp$^*$ and C. Guida$^*$ and E.
                      Ivanova$^*$ and A. De Jaime-Soguero and A. Jabali$^*$ and C.
                      Thomas and A. Salasova and O. Bernatík and C. Salio and S.
                      Horschitz$^*$ and M. Hasselblatt and M. Sassoe-Pognetto and
                      L. Čajánek and H. Ishikawa and H. Schroten and C. Schwerk
                      and S. P. Acebrón and P. Angel$^*$ and P. Koch$^*$ and A.
                      Patrizi$^*$},
      title        = {{A}ctivation of {W}nt/β-catenin signaling is critical for
                      the tumorigenesis of choroid plexus.},
      journal      = {Neuro-Oncology},
      volume       = {27},
      number       = {1},
      issn         = {1522-8517},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2024-01735},
      pages        = {106-122},
      year         = {2025},
      note         = {#EA:A320#LA:A320# / DKFZ/ZMBH Alliance / 2025 Jan
                      12;27(1):106-122},
      abstract     = {Choroid plexus (ChP) is the secretory epithelial structure
                      located in brain ventricles. Choroid plexus tumors (CPTs)
                      are rare neoplasms predominantly occurring in young patients
                      with intensified malignancy in children. CPT treatment is
                      hindered by insufficient knowledge of the tumor pathology
                      and limited availability of valid models.Genomic and
                      transcriptomic data from CPT patients were analyzed to
                      identify the putative pathological pathway. Cellular and
                      molecular techniques were employed to validate bioinformatic
                      results in CPT patient samples. Pharmacologic inhibition of
                      Wnt/β-catenin signaling was assessed in CPT cells.
                      Cell-based assays of ChP cell lines were performed following
                      CRISPR-Cas9-derived knockout and over-expression of
                      Wnt/β-catenin pathway genes. 3D CPT model was generated
                      through CRISPR-Cas9-derived knockout of APC.We discovered
                      that Wnt/β-catenin signaling is activated in human CPTs,
                      likely as a consequence of large-scale chromosomal
                      instability events of the CPT genomes. We demonstrated that
                      CPT-derived cells depend on autocrine Wnt/β-catenin
                      signaling for survival. Constitutive Wnt/β-catenin pathway
                      activation, either through knock-out of the negative
                      regulator APC or overexpression of the ligand WNT3A, induced
                      tumorigenic properties in ChP 2D in vitro models. Increased
                      activation of Wnt/β-catenin pathway in ChP organoids,
                      through treatment with a potent GSK3β inhibitor, reduced
                      the differentiation of mature ChP epithelia cells.
                      Remarkably, the depletion of APC was sufficient to induce
                      the oncogenic transformation of ChP organoids.Our research
                      identifies Wnt/β-catenin signaling as a critical driver of
                      CPT tumorigenesis and provides the first 3D in vitro model
                      for future pathological and therapeutic studies of CPT.},
      keywords     = {APC (Other) / Brain tumor (Other) / Wnt signaling (Other) /
                      choroid plexus organoid (Other) / rare childhood cancer
                      (Other)},
      cin          = {A320 / A340 / A100},
      ddc          = {610},
      cid          = {I:(DE-He78)A320-20160331 / I:(DE-He78)A340-20160331 /
                      I:(DE-He78)A100-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39215664},
      doi          = {10.1093/neuonc/noae176},
      url          = {https://inrepo02.dkfz.de/record/292488},
}