The zinc finger transcription factor ZFX is required for maintaining the tumorigenic potential of glioblastoma stem cells.

Published

Journal Article

Glioblastomas are highly lethal brain tumors containing tumor-propagating glioma stem cells (GSCs). The molecular mechanisms underlying the maintenance of the GSC phenotype are not fully defined. Here we demonstrate that the zinc finger and X-linked transcription factor (ZFX) maintains GSC self-renewal and tumorigenic potential by upregulating c-Myc expression. ZFX is differentially expressed in GSCs relative to non-stem glioma cells and neural progenitor cells. Disrupting ZFX by shRNA reduced c-Myc expression and potently inhibited GSC self-renewal and tumor growth. Ectopic expression of c-Myc to its endogenous level rescued the effects caused by ZFX disruption, supporting that ZFX controls GSC properties through c-Myc. Furthermore, ZFX binds to a specific sequence (GGGCCCCG) on the human c-Myc promoter to upregulate c-Myc expression. These data demonstrate that ZFX functions as a critical upstream regulator of c-Myc and plays essential roles in the maintenance of the GSC phenotype. This study also supports that c-Myc is a dominant driver linking self-renewal to malignancy.

Full Text

Duke Authors

Cited Authors

  • Fang, X; Huang, Z; Zhou, W; Wu, Q; Sloan, AE; Ouyang, G; McLendon, RE; Yu, JS; Rich, JN; Bao, S

Published Date

  • August 2014

Published In

Volume / Issue

  • 32 / 8

Start / End Page

  • 2033 - 2047

PubMed ID

  • 24831540

Pubmed Central ID

  • 24831540

Electronic International Standard Serial Number (EISSN)

  • 1549-4918

Digital Object Identifier (DOI)

  • 10.1002/stem.1730

Language

  • eng

Conference Location

  • United States