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@ARTICLE{Wirthschaft:136833,
      author       = {P. Wirthschaft$^*$ and J. Bode$^*$ and A. Simon$^*$ and E.
                      Hoffmann$^*$ and R. van Laack$^*$ and T. Krüwel$^*$ and F.
                      Dietrich$^*$ and D. Bucher$^*$ and A. Hahn and F. Sahm$^*$
                      and M. Breckwoldt$^*$ and F. T. Kurz and T. Hielscher$^*$
                      and B. Fischer$^*$ and N. Dross and C. Ruiz de Almodovar and
                      A. von Deimling$^*$ and C. Herold-Mende and C. Plass$^*$ and
                      S. Boulant$^*$ and B. P. O. Wiestler$^*$ and G.
                      Reifenberger$^*$ and P. Lichter$^*$ and W. Wick$^*$ and B.
                      Tews$^*$},
      title        = {{A} {PRDX}1-p38α heterodimer amplifies {MET}-driven
                      invasion of {IDH}-wildtype and {IDH}-mutant gliomas.},
      journal      = {International journal of cancer},
      volume       = {143},
      number       = {5},
      issn         = {0020-7136},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2018-01271},
      pages        = {1176 - 1187},
      year         = {2018},
      abstract     = {The Peroxiredoxin 1 (PRDX1) gene maps to chromosome arm 1p
                      and is hemizygously deleted and epigenetically silenced in
                      isocitrate dehydrogenase 1 or 2 (IDH)-mutant and
                      1p/19q-codeleted oligodendroglial tumors. In contrast,
                      IDH-wildtype astrocytic gliomas including glioblastomas
                      mostly lack epigenetic silencing and express PRDX1 protein.
                      In our study, we investigated how PRDX1 contributes to the
                      infiltrative growth of IDH-wildtype gliomas. Focusing on
                      p38α-dependent pathways, we analyzed clinical data from 133
                      patients of the NOA-04 trial cohort to look for differences
                      in the gene expression profiles of gliomas with wildtype or
                      mutant IDH. Biochemical interaction studies as well as in
                      vitro and ex vivo migration studies were used to establish a
                      biological role of PRDX1 in maintaining pathway activity.
                      Whole-brain high-resolution ultramicroscopy and survival
                      analyses of pre-clinical mouse models for IDH-wildtype
                      gliomas were then used for in vivo confirmation. Based on
                      clinical data, we found that the absence of PRDX1 is
                      associated with changes in the expression of MET/HGF
                      signaling components. PRDX1 forms a heterodimer with p38α
                      mitogen-activated protein kinase 14 (MAPK14), stabilizing
                      phospho-p38α in glioma cells. This process amplifies
                      hepatocyte growth factor (HGF)-mediated signaling and
                      stimulates actin cytoskeleton dynamics that promote glioma
                      cell migration. Whole-brain high-resolution ultramicroscopy
                      confirms these findings, indicating that PRDX1 promotes
                      glioma brain invasion in vivo. Finally, reduced expression
                      of PRDX1 increased survival in mouse glioma models. Thus,
                      our preclinical findings suggest that PRDX1 expression
                      levels may serve as a molecular marker for patients who
                      could benefit from targeted inhibition of MET/HGF
                      signaling.},
      cin          = {V077 / G370 / L101 / F140 / G380 / D170 / C060 / B210 /
                      C010 / L401 / B060},
      ddc          = {610},
      cid          = {I:(DE-He78)V077-20160331 / I:(DE-He78)G370-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)F140-20160331 /
                      I:(DE-He78)G380-20160331 / I:(DE-He78)D170-20160331 /
                      I:(DE-He78)C060-20160331 / I:(DE-He78)B210-20160331 /
                      I:(DE-He78)C010-20160331 / I:(DE-He78)L401-20160331 /
                      I:(DE-He78)B060-20160331},
      pnm          = {319H - Addenda (POF3-319H)},
      pid          = {G:(DE-HGF)POF3-319H},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29582423},
      doi          = {10.1002/ijc.31404},
      url          = {https://inrepo02.dkfz.de/record/136833},
}