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

Olga A. Guryanova, Qiulian Wu, Lin Cheng, Justin D. Lathia, Zhi Huang, Jinbo Yang, Jennifer MacSwords, Christine E. Eyler, Roger E. McLendon, John M. Heddleston, Weinian Shou, Dolores Hambardzumyan, Jeongwu Lee, Anita B. Hjelmeland, Andrew E. Sloan, Markus Bredel, George R. Stark, Jeremy N. Rich, Shideng Bao

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169 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)498-511
Number of pages14
JournalCancer Cell
Volume19
Issue number4
DOIs
StatePublished - Apr 12 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Guryanova, O. A., Wu, Q., Cheng, L., Lathia, J. D., Huang, Z., Yang, J., MacSwords, J., Eyler, C. E., McLendon, R. E., Heddleston, J. M., Shou, W., Hambardzumyan, D., Lee, J., Hjelmeland, A. B., Sloan, A. E., Bredel, M., Stark, G. R., Rich, J. N., & Bao, S. (2011). Nonreceptor Tyrosine Kinase BMX Maintains Self-Renewal and Tumorigenic Potential of Glioblastoma Stem Cells by Activating STAT3. Cancer Cell, 19(4), 498-511. https://doi.org/10.1016/j.ccr.2011.03.004