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@ARTICLE{Kufrin:300162,
      author       = {V. Kufrin and A. Seiler and S. Brilloff and H. Rothfuß and
                      S. Küchler and S. Schäfer and E. Rahimian and J.
                      Baumgarten and L. Ding and F. Buchholz and C. Ball$^*$ and
                      M. Bornhäuser and H. Glimm$^*$ and M. Bill$^*$ and A. A.
                      Wurm$^*$},
      title        = {{T}he histone modifier {KAT}2{A} presents a selective
                      target in a subset of well-differentiated
                      microsatellite-stable colorectal cancers.},
      journal      = {Cell death and differentiation},
      volume       = {32},
      issn         = {1350-9047},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2025-00648},
      pages        = {1259–1272},
      year         = {2025},
      note         = {32, pages 1259–1272},
      abstract     = {Lysine acetyltransferase 2 A (KAT2A) plays a pivotal role
                      in epigenetic gene regulation across various types of
                      cancer. In colorectal cancer (CRC), increased KAT2A
                      expression is associated with a more aggressive phenotype.
                      Our study aims to elucidate the molecular underpinnings of
                      KAT2A dependency in CRC and assess the consequences of KAT2A
                      depletion. We conducted a comprehensive analysis by
                      integrating CRISPR-Cas9 screening data with genomics,
                      transcriptomics, and global acetylation patterns in CRC cell
                      lines to pinpoint molecular markers indicative of KAT2A
                      dependency. Additionally, we characterized the phenotypic
                      effect of a CRISPR-interference-mediated KAT2A knockdown in
                      CRC cell lines and patient-derived 3D spheroid cultures.
                      Moreover, we assessed the effect of KAT2A depletion within a
                      patient-derived xenograft mouse model in vivo. Our findings
                      reveal that KAT2A dependency is closely associated with
                      microsatellite stability, lower mutational burden, and
                      increased molecular differentiation signatures in CRC,
                      independent of the KAT2A expression levels. KAT2A-dependent
                      CRC cells display higher gene expression levels and enriched
                      H3K27ac marks at gene loci linked to enterocytic
                      differentiation. Furthermore, loss of KAT2A leads to
                      decreased cell growth and viability in vitro and in vivo,
                      downregulation of proliferation- and stem cell-associated
                      genes, and induction of differentiation markers. Altogether,
                      our data show that a specific subset of CRCs with a more
                      differentiated phenotype relies on KAT2A. For these CRC
                      cases, KAT2A might represent a promising novel therapeutic
                      target.},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40140561},
      doi          = {10.1038/s41418-025-01479-7},
      url          = {https://inrepo02.dkfz.de/record/300162},
}