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

被引：285

作者：

Guryanova, Olga A. ^{[1
]}

Wu, Qiulian ^{[1
]}

Cheng, Lin ^{[1
,3
]}

Lathia, Justin D. ^{[1
]}

Huang, Zhi ^{[1
]}

Yang, Jinbo ^{[2
]}

MacSwords, Jennifer ^{[1
]}

Eyler, Christine E. ^{[1
,5
]}

McLendon, Roger E. ^{[6
]}

Heddleston, John M. ^{[1
]}

Shou, Weinian ^{[4
]}

Hambardzumyan, Dolores ^{[1
]}

Lee, Jeongwu ^{[1
]}

Hjelmeland, Anita B. ^{[1
]}

Sloan, Andrew E. ^{[7
]}

Bredel, Markus ^{[8
,9
,10
]}

Stark, George R. ^{[2
]}

Rich, Jeremy N. ^{[1
]}

Bao, Shideng ^{[1
]}

机构：

[1] Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA

[2] Cleveland Clin, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA

[3] Shanghai Jiao Tong Univ, Peoples Hosp 1, Expt Ctr, Shanghai 200080, Peoples R China

[4] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Dept Pediat, Indianapolis, IN 46202 USA

[5] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

[6] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[7] Case Western Reserve Univ, Univ Hosp, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA

[8] Univ Alabama Birmingham, Sch Med, Dept Radiat Oncol, Birmingham, AL 35249 USA

[9] Univ Alabama Birmingham, Sch Med, Dept Genet, Birmingham, AL 35249 USA

[10] Univ Alabama Birmingham, Sch Med, Dept Cell Biol, Birmingham, AL 35249 USA

来源：

CANCER CELL | 2011年 / 19卷 / 04期

关键词：

ENDOTHELIAL GROWTH-FACTOR; FACTOR RECEPTOR; CELLULAR-TRANSFORMATION; PROSTATE-CANCER; PH-DOMAIN; GLIOMA; ETK/BMX; ANGIOGENESIS; EXPRESSION; BIOLOGY;

D O I：

10.1016/j.ccr.2011.03.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：498 / 511

页数：14

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