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@ARTICLE{Malkomes:277740,
      author       = {P. Malkomes$^*$ and I. Lunger and E. Oppermann and J.
                      Lorenz and S. F. Faqar-Uz-Zaman and J. Han and S. Bothur and
                      P. Ziegler and K. Bankov and P. Wild and W. O. Bechstein and
                      M. A. Rieger$^*$},
      title        = {{T}ransglutaminase 2 is associated with adverse colorectal
                      cancer survival and represents a therapeutic target.},
      journal      = {Cancer gene therapy},
      volume       = {30},
      number       = {10},
      issn         = {0929-1903},
      address      = {New York, NY},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2023-01457},
      pages        = {1346-1354},
      year         = {2023},
      note         = {2023 Oct;30(10):1346-1354},
      abstract     = {Molecular markers for predicting prognosis of colorectal
                      cancer (CRC) patients are urgently needed for effective
                      disease management. We reported previously that the
                      multifunctional enzyme Transglutaminase 2 (TGM2) is
                      essential for CRC cell survival by inactivation of the tumor
                      suppressor p53. Based on these data, we determined the
                      clinical relevance of TGM2 expression and explored its
                      potential as prognostic marker and therapeutic target in
                      CRC. We profiled TGM2 protein expression in tumor samples of
                      279 clinically characterized CRC patients using
                      immunohistochemical staining. TGM2 expression was
                      upregulated in matched tumor samples in comparison to normal
                      tissue. A strong TGM2 expression was associated with
                      advanced tumor stages and predicted worse prognosis
                      regarding progression-free and overall-survival, even at
                      early stages. Inhibition of TGM2 in CRC cell lines by the
                      inhibitors LDN27219 and Tyrphostin resulted in a strong
                      reduction of cancer cell proliferation and tumorsphere
                      formation in vitro by induction of p53-mediated apoptosis.
                      Primary patient-derived tumorsphere formation was
                      significantly reduced by inhibition of TGM2. Treatment of
                      mice with TGM2 inhibitors exhibited a significant
                      deceleration of tumor progression. Our data indicate that
                      high TGM2 expression in CRC is associated with worse
                      prognosis and may serve as a therapeutic target in CRC
                      patients with strong TGM2 expression.},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37443286},
      doi          = {10.1038/s41417-023-00641-y},
      url          = {https://inrepo02.dkfz.de/record/277740},
}