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@ARTICLE{Dyberg:148855,
      author       = {C. Dyberg and T. Andonova and T. K. Olsen and B. Brodin and
                      M. Kool$^*$ and P. Kogner and J. I. Johnsen and M.
                      Wickström},
      title        = {{I}nhibition of {R}ho-{A}ssociated {K}inase {S}uppresses
                      {M}edulloblastoma {G}rowth.},
      journal      = {Cancers},
      volume       = {12},
      number       = {1},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2020-00047},
      pages        = {73},
      year         = {2020},
      note         = {Cancers 2020, 12(1), 73;
                      https://doi.org/10.3390/cancers12010073},
      abstract     = {Medulloblastoma is one of the most common malignant brain
                      tumor types in children, with an overall survival of $70\%.$
                      Mortality is associated with metastatic relapsed tumors.
                      Rho-associated kinases (ROCKs), important for
                      epithelial-mesenchymal transition (EMT) and proper nervous
                      system development, have previously been identified as a
                      promising drug target to inhibit cancer growth and
                      metastatic spread. Here, we show that ROCKs are expressed in
                      medulloblastoma, with higher ROCK2 mRNA expression in
                      metastatic compared to non-metastatic tumors. By evaluating
                      three ROCK inhibitors in a panel of medulloblastoma cell
                      lines we demonstrated that medulloblastoma cells were
                      sensitive for pharmacological ROCK inhibition. The specific
                      ROCK inhibitor RKI-1447 inhibited the tumorigenicity in
                      medulloblastoma cells as well as impeded cell migration and
                      invasion. Differential gene expression analysis suggested
                      that ROCK inhibition was associated with the downregulation
                      of signaling pathways important in proliferation and
                      metastasis e.g., TNFα via NFκβ, TGFβ, and EMT.
                      Expression of key proteins in these pathways such as RHOA,
                      RHOB, JUN, and vimentin was downregulated in ROCK inhibited
                      cells. Finally, we showed that ROCK inhibition by RKI-1447
                      suppressed medulloblastoma growth and proliferation in vivo.
                      Collectively, our results suggest that ROCK inhibition
                      presents a potential new therapeutic option in
                      medulloblastoma, especially for children with metastatic
                      disease.},
      cin          = {B062 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31888022},
      doi          = {10.3390/cancers12010073},
      url          = {https://inrepo02.dkfz.de/record/148855},
}