Krüppel-like family of transcription factor 9, a differentiation- associated transcription factor, suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells

Mingyao Ying, Yingying Sang, Yunqing Li, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Angelo L. Vescovi, Charles G. Eberhart, Shuli Xia, John Laterra

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Tumor-initiating stem cells (alternatively called cancer stem cells, CSCs) are a subpopulation of tumor cells that plays unique roles in tumor propagation, therapeutic resistance, and tumor recurrence. It is becoming increasingly important to understand the molecular signaling that regulates the self-renewal and differentiation of CSCs. Transcription factors are critical for the regulation of normal and neopolastic stem cells. Here, we examined the expression and function of the Krüppel-like family of transcription factors (KLFs) in human glioblastoma (GBM)-derived neurosphere lines and low-passage primary GBM-derived neurospheres that are enriched for tumor-initiating stem cells. We identify KLF9 as a relatively unique differentiation-induced transcription factor in GBM-derived neurospheres. KLF9 is shown to induce neurosphere cell differentiation, inhibit neurosphere formation, and inhibit neurosphere-derived xenograft growth in vivo. We also show that KLF9 regulates GBM neurosphere cells by binding to the Notch1 promoter and suppressing Notch1 expression and downstream signaling. Our results show for the first time that KLF9 has differentiating and tumor-suppressing functions in tumor-initiating stem cells.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalStem Cells
Volume29
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Cancer stem cell
  • Differentiation
  • Notch signaling
  • Retinoic acid
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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