Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the 
Polycomb-repressive complex 2 (PRC2) that epigenetically silences gene 
transcription through histone H3 lysine trimethylation (H3K27me3). EZH2 has been 
implicated in stem cell maintenance and is overexpressed in hematological and 
solid malignancie`s including malignant glioma. EZH2 is thought to promote tumor 
progression by silencing tumor suppressor genes. Hence pharmacological 
disruption of the PRC2 is an attractive therapeutic strategy for cancer 
treatment. Here we show that EZH2 is expressed in human glioma and correlates 
with malignancy. Silencing of EZH2 reduced glioma cell proliferation and 
invasiveness. While we did not observe induction of cell cycle-associated tumor 
suppressor genes by silencing or pharmacological inhibition of EZH2, microarray 
analyses demonstrated a strong transcriptional reduction of the AXL receptor 
kinase. Neither histone nor DNA methylation appeared to be involved in the 
positive regulation of AXL by EZH2. Silencing AXL mimicked the antiinvasive 
effects of EZH2 knockdown. Finally, AXL expression is found in human gliomas 
with high EZH2 expression. Collectively these data suggest that EZH2 drives 
glioma invasiveness via transcriptional control of AXL independent of histone or 
DNA methylation.