% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Tomek:141883,
      author       = {P. Tomek and S. K. Gore and C. L. Potts and C. G. Print and
                      M. A. Black and A. Hallermayr and M. Kilian$^*$ and E.
                      Sattlegger and L.-M. Ching},
      title        = {{I}mprinted and ancient gene: a potential mediator of
                      cancer cell survival during tryptophan deprivation.},
      journal      = {Cell communication and signaling},
      volume       = {16},
      number       = {1},
      issn         = {1478-811X},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DKFZ-2018-02140},
      pages        = {88},
      year         = {2018},
      abstract     = {Depletion of tryptophan and the accumulation of tryptophan
                      metabolites mediated by the immunosuppressive enzyme
                      indoleamine 2,3-dioxygenase 1 (IDO1), trigger immune cells
                      to undergo apoptosis. However, cancer cells in the same
                      microenvironment appear not to be affected. Mechanisms
                      whereby cancer cells resist accelerated tryptophan
                      degradation are not completely understood. We hypothesize
                      that cancer cells co-opt IMPACT (the product of IMPrinted
                      and AnCienT gene), to withstand periods of tryptophan
                      deficiency.A range of bioinformatic techniques including
                      correlation and gene set variation analyses was applied to
                      genomic datasets of cancer (The Cancer Genome Atlas) and
                      normal (Genotype Tissue Expression Project) tissues to
                      investigate IMPACT's role in cancer. Survival of
                      IMPACT-overexpressing GL261 glioma cells and their wild type
                      counterparts cultured in low tryptophan media was assessed
                      using fluorescence microscopy and MTT bio-reduction assay.
                      Expression of the Integrated Stress Response proteins was
                      measured using Western blotting.We found IMPACT to be
                      upregulated and frequently amplified in a broad range of
                      clinical cancers relative to their non-malignant tissue
                      counterparts. In a subset of clinical cancers, high IMPACT
                      expression associated with decreased activity of pathways
                      and genes involved in stress response and with increased
                      activity of translational regulation such as the mTOR
                      pathway. Experimental studies using the GL261 glioma line
                      showed that cells engineered to overexpress IMPACT, gained a
                      survival advantage over wild-type lines when cultured under
                      limiting tryptophan concentrations. No significant
                      difference in the expression of proteins in the Integrated
                      Stress Response pathway was detected in tryptophan-deprived
                      GL261 IMPACT-overexpressors compared to that in wild-type
                      cells. IMPACT-overexpressing GL261 cells but not their
                      wild-type counterparts, showed marked enlargement of their
                      nuclei and cytoplasmic area when stressed by tryptophan
                      deprivation.The bioinformatics data together with our
                      laboratory studies, support the hypothesis that IMPACT
                      mediates a protective mechanism allowing cancer cells to
                      overcome microenvironmental stresses such as tryptophan
                      deficiency.},
      cin          = {G160},
      ddc          = {570},
      cid          = {I:(DE-He78)G160-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30466445},
      pmc          = {pmc:PMC6251197},
      doi          = {10.1186/s12964-018-0301-7},
      url          = {https://inrepo02.dkfz.de/record/141883},
}