Open AccessThe Zinc Finger Transcription Factor ZFX Is Required for Maintaining the Tumorigenic Potential of Glioblastoma Stem Cells
Author(s) -
Fang Xiaoguang,
Huang Zhi,
Zhou Wenchao,
Wu Qiulian,
Sloan Andrew E.,
Ouyang Gaoliang,
McLendon Roger E.,
Yu Jennifer S.,
Rich Jeremy N.,
Bao Shideng
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1730
Subject(s) - biology , zinc finger , transcription factor , cancer research , stem cell , zinc finger transcription factor , ectopic expression , glioma , progenitor cell , proto oncogene proteins c myc , phenotype , neural stem cell , microbiology and biotechnology , cell culture , genetics , gene
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. S tem C ells 2014;32:2033–2047