title: Nonreceptor tyrosine kinase BMX maintains self-renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3.
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.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Guryanova
authors.forename: Qiulian
authors.initials: Q
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.forename: Zhi
authors.initials: Z
authors.lastname: Huang
authors.forename: Jinbo
authors.initials: J
authors.lastname: Yang
authors.forename: Jennifer
authors.initials: J
authors.lastname: MacSwords
authors.forename: Christine E
authors.initials: CE
authors.lastname: Eyler
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: John M
authors.initials: JM
authors.lastname: Heddleston
authors.forename: Weinian
authors.initials: W
authors.lastname: Shou
authors.forename: Dolores
authors.initials: D
authors.lastname: Hambardzumyan
authors.forename: Jeongwu
authors.initials: J
authors.lastname: Lee
authors.forename: Anita B
authors.initials: AB
authors.lastname: Hjelmeland
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
authors.forename: Markus
authors.initials: M
authors.lastname: Bredel
authors.forename: George R
authors.initials: GR
authors.lastname: Stark
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: Shideng
authors.initials: S
authors.lastname: Bao
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D000076104:Oligodendrocyte Transcription Factor 2; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D019947:Receptors, Interleukin-6 / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011505:Protein-Tyrosine Kinases; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; C405708:OLIG2 protein, human; C494086:STAT3 protein, human; C492367:BMX protein, human