RRC ID 31980
Author Kim SN, Jeibmann A, Halama K, Witte HT, Wälte M, Matzat T, Schillers H, Faber C, Senner V, Paulus W, Klämbt C.
Title ECM stiffness regulates glial migration in Drosophila and mammalian glioma models.
Journal Development
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.
Volume 141(16)
Pages 3233-42
Published 2014-8-1
DOI 10.1242/dev.106039
PII dev.106039
PMID 25063458
MeSH Animals Animals, Genetically Modified Base Sequence Cell Line, Tumor Cell Movement Compound Eye, Arthropod / embryology* Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / metabolism Drosophila melanogaster / physiology* Extracellular Matrix / metabolism Extracellular Matrix / physiology* Female Gene Expression Regulation, Developmental Glioblastoma / metabolism Humans Integrins / metabolism Mice Mice, Nude Molecular Sequence Data Neoplasm Transplantation Neuroglia / cytology* Protein-Lysine 6-Oxidase / genetics Protein-Lysine 6-Oxidase / physiology* Signal Transduction
IF 5.611
Times Cited 38
WOS Category DEVELOPMENTAL BIOLOGY
Resource
Drosophila 11335R-3