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@ARTICLE{Reissland:294136,
      author       = {M. Reissland and O. Hartmann and S. Tauch$^*$ and J. M.
                      Bugter and C. Prieto-Garcia and C. Schulte and S. Loebbert
                      and D. Solvie and E. Bitman-Lotan and A. Narain and A.-C.
                      Jacomin and C. Schuelein-Voelk and C. T. Fuss and N. Pahor
                      and C. Ade and V. Buck and M. Potente and V. Li and G. Beliu
                      and A. Wiegering and T. Grossmann and M. Eilers and E. Wolf
                      and H. Maric and M. Rosenfeldt and M. M. Maurice and I.
                      Dikic and P. Gallant and A. Orian and M. E. Diefenbacher},
      title        = {{USP}10 drives cancer stemness and enables super-competitor
                      signalling in colorectal cancer.},
      journal      = {Oncogene},
      volume       = {43},
      number       = {50},
      issn         = {0950-9232},
      address      = {London},
      publisher    = {Springer Nature},
      reportid     = {DKFZ-2024-02134},
      pages        = {3645-3659},
      year         = {2024},
      note         = {#EA:A100# / 2024 Dec;43(50):3645-3659},
      abstract     = {The contribution of deubiquitylating enzymes (DUBs) to
                      β-Catenin stabilization in intestinal stem cells and
                      colorectal cancer (CRC) is poorly understood. Here, and by
                      using an unbiassed screen, we discovered that the DUB USP10
                      stabilizes β-Catenin specifically in APC-truncated CRC in
                      vitro and in vivo. Mechanistic studies, including in vitro
                      binding together with computational modelling, revealed that
                      USP10 binding to β-Catenin is mediated via the unstructured
                      N-terminus of USP10 and is outcompeted by intact APC,
                      favouring β-catenin degradation. However, in APC-truncated
                      cancer cells USP10 binds to β-catenin, increasing its
                      stability which is critical for maintaining an
                      undifferentiated tumour identity. Elimination of USP10
                      reduces the expression of WNT and stem cell signatures and
                      induces the expression of differentiation genes. Remarkably,
                      silencing of USP10 in murine and patient-derived CRC
                      organoids established that it is essential for NOTUM
                      signalling and the APC super competitor-phenotype, reducing
                      tumorigenic properties of APC-truncated CRC. These findings
                      are clinically relevant as patient-derived organoids are
                      highly dependent on USP10, and abundance of USP10 correlates
                      with poorer prognosis of CRC patients. Our findings reveal,
                      therefore, a role for USP10 in CRC cell identity, stemness,
                      and tumorigenic growth by stabilising β-Catenin, leading to
                      aberrant WNT signalling and degradation resistant tumours.
                      Thus, USP10 emerges as a unique therapeutic target in APC
                      truncated CRC.},
      cin          = {A100},
      ddc          = {610},
      cid          = {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:39443725},
      doi          = {10.1038/s41388-024-03141-x},
      url          = {https://inrepo02.dkfz.de/record/294136},
}