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Cancer Stem Cells
Article first published online: 28 JAN 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 1, pages 20–31, January 2011
How to Cite
Ying, M., Sang, Y., Li, Y., Guerrero-Cazares, H., Quinones-Hinojosa, A., Vescovi, A. L., Eberhart, C. G., Xia, S. and Laterra, J. (2011), Krüppel-Like Family of Transcription Factor 9, a Differentiation-Associated Transcription Factor, Suppresses Notch1 Signaling and Inhibits Glioblastoma-Initiating Stem Cells. STEM CELLS, 29: 20–31. doi: 10.1002/stem.561
Author contributions: M.Y.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript; Y.S., Y.L., and S.X.: collection and assembly of data, final approval of manuscript; H.G.-C., A.Q.-H., A.L.V., and C.G.E.: providing material, final approval of manuscript; J.L.: conception and design, financial support, administrative support, data analysis and interpretation, manuscript writing, final approval of manuscript.
First published online in STEM CELLS EXPRESS November 18, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 28 JAN 2011
- Article first published online: 28 JAN 2011
- Accepted manuscript online: 18 NOV 2010 08:51AM EST
- Manuscript Accepted: 30 OCT 2010
- Manuscript Received: 27 JUL 2010
- Cancer stem cell;
- Retinoic acid;
- Transcription factor;
- Notch signaling
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. STEM CELLS 2011;29:20–31