Author/Authors :
Guryanova، نويسنده , , Olga A. and Wu، نويسنده , , Qiulian and Cheng، نويسنده , , Lin and Lathia، نويسنده , , Justin D. and Huang، نويسنده , , Zhi and Yang، نويسنده , , Jinbo and MacSwords، نويسنده , , Jennifer and Eyler، نويسنده , , Christine E. and McLendon، نويسنده , , Roger E. and Heddleston، نويسنده , , John M. and Shou، نويسنده , , Weinian and Hambardzumyan، نويسنده , , Dolores and Lee، نويسنده , , Jeongwu and Hjelmeland، نويسنده , , Anita B. and Sloan، نويسنده , , Andrew E. and Bredel، نويسنده , , Markus and Stark، نويسنده , , George R. and Rich، نويسنده , , Jeremy N. and Bao، نويسنده , , Shideng، نويسنده ,
Abstract :
Summary
astomas display cellular hierarchies containing tumor-propagating glioblastoma stem cells (GSCs). STAT3 is a critical signaling node in GSC maintenance but molecular mechanisms underlying STAT3 activation in GSCs are poorly defined. Here we demonstrate that the bone marrow X-linked (BMX) nonreceptor tyrosine kinase activates STAT3 signaling to maintain self-renewal and tumorigenic potential of GSCs. BMX is differentially expressed in GSCs relative to nonstem cancer cells and neural progenitors. BMX knockdown potently inhibited STAT3 activation, expression of GSC transcription factors, and growth of GSC-derived intracranial tumors. Constitutively active STAT3 rescued the effects of BMX downregulation, supporting that BMX signals through STAT3 in GSCs. These data demonstrate that BMX represents a GSC therapeutic target and reinforces the importance of STAT3 signaling in stem-like cancer phenotypes.
