title: ECM stiffness regulates glial migration in Drosophila and mammalian glioma models.
abstract: Cell migration is an important feature of glial cells. Here, we used the Drosophila eye disc to decipher the molecular network controlling glial migration. We stimulated glial motility by pan-glial PDGF receptor (PVR) activation and identified several genes acting downstream of PVR. Drosophila lox is a non-essential gene encoding a secreted protein that stiffens the extracellular matrix (ECM). Glial-specific knockdown of Integrin results in ECM softening. Moreover, we show that lox expression is regulated by Integrin signaling and vice versa, suggesting that a positive-feedback loop ensures a rigid ECM in the vicinity of migrating cells. The general implication of this model was tested in a mammalian glioma model, where a Lox-specific inhibitor unraveled a clear impact of ECM rigidity in glioma cell migration.
authors: Institute of Neurobiology, University of Münster, Münster 48149, Germany.
authors: Su Na
authors: SN
authors: Kim
authors: Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
authors: Astrid
authors: A
authors: Jeibmann
authors: Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
authors: Kathrin
authors: K
authors: Halama
authors: Institute of Neurobiology, University of Münster, Münster 48149, Germany Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
authors: Hanna Teresa
authors: HT
authors: Witte
authors: Institute of Physiology II, University Hospital Münster, Münster 48149, Germany.
authors: Mike
authors: M
authors: Wälte
authors: Institute of Neurobiology, University of Münster, Münster 48149, Germany.
authors: Till
authors: T
authors: Matzat
authors: Institute of Physiology II, University Hospital Münster, Münster 48149, Germany.
authors: Hermann
authors: H
authors: Schillers
authors: Department of Clinical Radiology, University Hospital Münster, Münster 48149, Germany.
authors: Cornelius
authors: C
authors: Faber
authors: Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
authors: Volker
authors: V
authors: Senner
authors: Institute of Neuropathology, University Hospital Münster, Münster 48149, Germany.
authors: Werner
authors: W
authors: Paulus
authors: Institute of Neurobiology, University of Münster, Münster 48149, Germany klaembt@uni-muenster.de.
authors: Christian
authors: C
authors: Klämbt
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D054910:Compound Eye, Arthropod / Q000196:embryology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005909:Glioblastoma / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009457:Neuroglia / Q000166:cytology*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D016023:Integrins; D008249:Protein-Lysine 6-Oxidase
keywords: Drosophila; Extracellular matrix; Glial cell migration; Human; Lox; Lysyl oxidase; Mouse; PDGF-receptor; PVR