Nonreceptor Tyrosine Kinase BMX Maintains Self-Renewal and Tumorigenic Potential of Glioblastoma Stem Cells by Activating STAT3

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• 作者：Olga  ; A. Guryanova¹ ; Qiulian Wu¹ ; Lin Cheng¹ ; ³ ; Justin  ; D. Lathia¹ ; Zhi Huang¹ ; Jinbo Yang² ; Jennifer MacSwords¹ ; Christine  ; E. Eyler¹ ; ⁵ ; Roger  ; E. McLendon⁶ ; John  ; M. Heddleston¹ ; Weinian Shou⁴ ; Dolores Hambardzumyan¹ ; Jeongwu Lee¹ ; Anita  ; B. Hjelmeland¹ ; Andrew  ; E. Sloan⁷ ; Markus Bredel⁸ ; George  ; R. Stark² ; Jeremy  ; N. Rich¹ ; ^{richj@ccf.org} ; Shideng Bao¹ ; ^baos@ccf.org
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：12 April 2011
• 年：2011
• 卷：19
• 期：4
• 页码：498-511
• 全文大小：2847 K

文摘

Summary

Glioblastomas 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.