Author/Authors :
Lee، نويسنده , , Jeongwu and Son، نويسنده , , Myung Jin and Woolard، نويسنده , , Kevin and Donin، نويسنده , , Nicholas M. and Li، نويسنده , , Aiguo and Cheng، نويسنده , , Chui H. and Kotliarova، نويسنده , , Svetlana and Kotliarov، نويسنده , , Yuri and Walling، نويسنده , , Jennifer T. Ahn، نويسنده , , Susie C. Kim MD، نويسنده , , Misuk and Totonchy، نويسنده , , Mariam and Cusack، نويسنده , , Thomas and Ene، نويسنده , , Chibawanye and Ma، نويسنده , , Hilary and Su، نويسنده , , Qin and Zenklusen، نويسنده , , Jean Claude and Zhang، نويسنده , , Wei and Maric، نويسنده , , Dragan and Fine، نويسنده , , Howard A.، نويسنده ,
Abstract :
Summary
e similarities between tumor-initiating cells with stem-like properties (TICs) and normal neural stem cells, we hypothesized that there may be differences in their differentiation potentials. We now demonstrate that both bone morphogenetic protein (BMP)-mediated and ciliary neurotrophic factor (CNTF)-mediated Jak/STAT-dependent astroglial differentiation is impaired due to EZH2-dependent epigenetic silencing of BMP receptor 1B (BMPR1B) in a subset of glioblastoma TICs. Forced expression of BMPR1B either by transgene expression or demethylation of the promoter restores their differentiation capabilities and induces loss of their tumorigenicity. We propose that deregulation of the BMP developmental pathway in a subset of glioblastoma TICs contributes to their tumorigenicity both by desensitizing TICs to normal differentiation cues and by converting otherwise cytostatic signals to proproliferative signals.
