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@ARTICLE{Moussa:294358,
      author       = {A. Moussa$^*$ and M. R. Cosenza$^*$ and T. Wohlfromm$^*$
                      and K. Brobeil$^*$ and A. Hill$^*$ and A. Patrizi$^*$ and K.
                      Müller-Decker$^*$ and T. Holland-Letz$^*$ and A. Jauch and
                      B. Kraft$^*$ and A. Krämer$^*$},
      title        = {{STIL} overexpression shortens lifespan and reduces tumor
                      formation in mice.},
      journal      = {PLoS Genetics},
      volume       = {20},
      number       = {10},
      issn         = {1553-7390},
      address      = {San Francisco, Calif.},
      publisher    = {Public Library of Science},
      reportid     = {DKFZ-2024-02191},
      pages        = {e1011460 -},
      year         = {2024},
      note         = {#EA:A360#LA:A360#},
      abstract     = {Centrosomes are the major microtubule organizing centers of
                      animal cells. Supernumerary centrosomes are a common feature
                      of human tumors and associated with karyotype abnormalities
                      and aggressive disease, but whether they are cause or
                      consequence of cancer remains controversial. Here, we
                      analyzed the consequences of centrosome amplification by
                      generating transgenic mice in which centrosome numbers can
                      be increased by overexpression of the structural centrosome
                      protein STIL. We show that STIL overexpression induces
                      centrosome amplification and aneuploidy, leading to
                      senescence, apoptosis, and impaired proliferation in mouse
                      embryonic fibroblasts, and microcephaly with increased
                      perinatal lethality and shortened lifespan in mice.
                      Importantly, both overall tumor formation in mice with
                      constitutive, global STIL overexpression and chemical skin
                      carcinogenesis in animals with inducible, skin-specific STIL
                      overexpression were reduced, an effect that was not rescued
                      by concomitant interference with p53 function. These results
                      suggest that supernumerary centrosomes impair proliferation
                      in vitro as well as in vivo, resulting in reduced lifespan
                      and delayed spontaneous as well as carcinogen-induced tumor
                      formation.},
      cin          = {A360 / A320 / W420 / C060},
      ddc          = {610},
      cid          = {I:(DE-He78)A360-20160331 / I:(DE-He78)A320-20160331 /
                      I:(DE-He78)W420-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39466849},
      doi          = {10.1371/journal.pgen.1011460},
      url          = {https://inrepo02.dkfz.de/record/294358},
}