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@ARTICLE{Fabian:119916,
      author       = {J. Fabian$^*$ and M. Lodrini$^*$ and I. Oehme$^*$ and M. C.
                      Schier$^*$ and T. Thole$^*$ and T. Hielscher$^*$ and A.
                      Kopp-Schneider$^*$ and L. Opitz and D. Capper$^*$ and A. von
                      Deimling$^*$ and I. Wiegand$^*$ and T. Milde$^*$ and U.
                      Mahlknecht and F. Westermann$^*$ and O. Popanda$^*$ and F.
                      Roels and B. Hero and F. Berthold and M. Fischer and A. E.
                      Kulozik and O. Witt$^*$ and H. E. Deubzer$^*$},
      title        = {{GRHL}1 acts as tumor suppressor in neuroblastoma and is
                      negatively regulated by {MYCN} and {HDAC}3.},
      journal      = {Cancer research},
      volume       = {74},
      number       = {9},
      issn         = {1538-7445},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2017-00507},
      pages        = {2604 - 2616},
      year         = {2014},
      abstract     = {Neuroblastoma is an embryonic solid tumor of neural crest
                      origin and accounts for $11\%$ of all cancer-related deaths
                      in children. Novel therapeutic strategies are therefore
                      urgently required. MYCN oncogene amplification, which occurs
                      in $20\%$ of neuroblastomas, is a hallmark of high risk.
                      Here, we aimed to exploit molecular mechanisms that can be
                      pharmacologically addressed with epigenetically modifying
                      drugs, such as histone deacetylase (HDAC) inhibitors.
                      Grainyhead-like 1 (GRHL1), a gene critical for Drosophila
                      neural development, belonged to the genes most strongly
                      responding to HDAC inhibitor treatment of neuroblastoma
                      cells in a genome-wide screen. An increase in the histone H4
                      pan-acetylation associated with its promoter preceded
                      transcriptional activation. Physically adjacent, HDAC3 and
                      MYCN colocalized to the GRHL1 promoter and repressed its
                      transcription. High-level GRHL1 expression in primary
                      neuroblastomas correlated on transcriptional and
                      translational levels with favorable patient survival and
                      established clinical and molecular markers for favorable
                      tumor biology, including lack of MYCN amplification.
                      Enforced GRHL1 expression in MYCN-amplified neuroblastoma
                      cells with low endogenous GRHL1 levels abrogated
                      anchorage-independent colony formation, inhibited
                      proliferation, and retarded xenograft growth in mice. GRHL1
                      knockdown in MYCN single-copy cells with high endogenous
                      GRHL1 levels promoted colony formation. GRHL1 regulated 170
                      genes genome-wide, and most were involved in pathways
                      regulated during neuroblastomagenesis, including nervous
                      system development, proliferation, cell-cell adhesion, cell
                      spreading, and cellular differentiation. In summary, the
                      data presented here indicate a significant role of HDAC3 in
                      the MYCN-mediated repression of GRHL1 and suggest drugs that
                      block HDAC3 activity and suppress MYCN expression as
                      promising candidates for novel treatment strategies of
                      high-risk neuroblastoma.},
      keywords     = {Antineoplastic Agents (NLM Chemicals) / GRHL1 protein,
                      human (NLM Chemicals) / Histone Deacetylase Inhibitors (NLM
                      Chemicals) / Hydroxamic Acids (NLM Chemicals) / Indoles (NLM
                      Chemicals) / MYCN protein, human (NLM Chemicals) / N-Myc
                      Proto-Oncogene Protein (NLM Chemicals) / Nuclear Proteins
                      (NLM Chemicals) / Oncogene Proteins (NLM Chemicals) /
                      Repressor Proteins (NLM Chemicals) / panobinostat (NLM
                      Chemicals) / Histone Deacetylases (NLM Chemicals) / histone
                      deacetylase 3 (NLM Chemicals)},
      cin          = {G340 / C060 / G380 / B087 / C010},
      ddc          = {610},
      cid          = {I:(DE-He78)G340-20160331 / I:(DE-He78)C060-20160331 /
                      I:(DE-He78)G380-20160331 / I:(DE-He78)B087-20160331 /
                      I:(DE-He78)C010-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24419085},
      doi          = {10.1158/0008-5472.CAN-13-1904},
      url          = {https://inrepo02.dkfz.de/record/119916},
}