例如:"lncRNA", "apoptosis", "WRKY"

RhoA regulates translation of the Nogo-A decoy SPARC in white matter-invading glioblastomas.

Acta Neuropathol. 2019 Aug;138(2):275-293. Epub 2019 May 06
Peter Wirthschaft 1 , Julia Bode 1 , Himanshu Soni 1 , Fabio Dietrich 1 , Thomas Krüwel 1 , Bernd Fischer 2 , Christiane B Knobbe-Thomsen 3 , Giulia Rossetti 4 , Andreas Hentschel 5 , Norman Mack 6 , Kai Schönig 7 , Michael O Breckwoldt 8 , André Schmandke 9 , Stefan Pusch 10 , Jan Medenbach 11 , Martin Bendszus 12 , Martin E Schwab 13 , Andreas von Deimling 10 , Marcel Kool 6 , Christel Herold-Mende 14 , Guido Reifenberger 15 , Robert Ahrends 5 , Björn Tews 16
Peter Wirthschaft 1 , Julia Bode 1 , Himanshu Soni 1 , Fabio Dietrich 1 , Thomas Krüwel 1 , Bernd Fischer 2 , Christiane B Knobbe-Thomsen 3 , Giulia Rossetti 4 , Andreas Hentschel 5 , Norman Mack 6 , Kai Schönig 7 , Michael O Breckwoldt 8 , André Schmandke 9 , Stefan Pusch 10 , Jan Medenbach 11 , Martin Bendszus 12 , Martin E Schwab 13 , Andreas von Deimling 10 , Marcel Kool 6 , Christel Herold-Mende 14 , Guido Reifenberger 15 , Robert Ahrends 5 , Björn Tews 16
+ et al

[No authors listed]

Author information
  • 1 Molecular Mechanisms of Tumor Invasion (V077), DKFZ, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
  • 2 Computational Genome Biology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
  • 3 Department of Neuropathology, Heinrich Heine University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
  • 4 Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
  • 5 Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V, Otto-Hahn-Str. 6b, 44227, Dortmund, Germany.
  • 6 Division of Pediatric Neurooncology, DKFZ, Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.
  • 7 Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, J 5, 68159, Mannheim, Germany.
  • 8 Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, DKFZ, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
  • 9 Max Planck Institute for Demographic Research, Konrad-Zuse-Straße 1, 18057, Rostock, Germany.
  • 10 Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and DKTK, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
  • 11 Biochemistry I-Institute for Biochemistry, Genetics and Microbiology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany.
  • 12 Neuroradiology Department, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
  • 13 Department of Health Sciences and Technology, ETH Zurich, Universitätstrasse 2, 8092, Zurich, Switzerland.
  • 14 Division of Experimental Neurosurgery, Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany.
  • 15 German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, 40225, Düsseldorf, Germany.
  • 16 Björn Tews, AbbVie Deutschland GmbH & Co.KG, Wiesbaden, Germany. bjoern.tews@web.de.

摘要


Glioblastomas strongly invade the brain by infiltrating into the white matter along myelinated nerve fiber tracts even though the myelin protein Nogo-A prevents cell migration by activating inhibitory RhoA signaling. The mechanisms behind this long-known phenomenon remained elusive so far, precluding a targeted therapeutic intervention. This study demonstrates that the prevalent activation of AKT in gliomas increases the ER protein-folding capacity and enables tumor cells to utilize a side effect of RhoA activation: the perturbation of the IRE1α-mediated decay of mRNA. Once translation is initiated, glioblastoma cells rapidly secrete duanyu1842RC to block Nogo-A from inhibiting migration via RhoA. By advanced ultramicroscopy for studying single-cell invasion in whole, undissected mouse brains, we show that gliomas require duanyu1842RC for invading into white matter structures. duanyu1842RC depletion reduces tumor dissemination that significantly prolongs survival and improves response to cytostatic therapy. Our finding of a novel RhoA-IRE1 axis provides a druggable target for interfering with duanyu1842RC production and underscores its therapeutic value.

KEYWORDS: AKT, ENTPD5, Glioblastoma, IRE1α, Invasion, Nogo-A, Post-transcriptional regulation, RhoA, SPARC, White matter