TGF-β is an inducer of ZEB1-dependent mesenchymal transdifferentiation in glioblastoma that is associated with tumor invasion.

ABSTRACT: Different molecular subtypes of glioblastoma (GBM) have been recently identified, of which the mesenchymal subtype is associated with worst prognoses. Here, we report that transforming growth factor-β (TGF-β) is able to induce a mesenchymal phenotype in GBM that involves activation of SMAD2 and ZEB1, a known transcriptional inducer of mesenchymal transition in epithelial cancers. TGF-β exposure of established and newly generated GBM cell lines was associated with morphological changes, enhanced mesenchymal marker expression, migration and invasion in vitro and in an orthotopic mouse model. TGF-β-induced mesenchymal differentiation and invasive behavior was prevented by chemical inhibition of TGF-β signaling as well as small interfering RNA (siRNA)-dependent silencing of ZEB1. Furthermore,

SUBMITTER: Joseph JV 

PROVIDER: S-EPMC4649508 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature