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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2011 Apr 13

PMID 21481791

Citations 169

Authors

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

Affiliations

Soon will be listed here.

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.

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