TY - JOUR
T1 - Krüppel-like family of transcription factor 9, a differentiation- associated transcription factor, suppresses Notch1 signaling and inhibits glioblastoma-initiating stem cells
AU - Ying, Mingyao
AU - Sang, Yingying
AU - Li, Yunqing
AU - Guerrero-Cazares, Hugo
AU - Quinones-Hinojosa, Alfredo
AU - Vescovi, Angelo L.
AU - Eberhart, Charles G.
AU - Xia, Shuli
AU - Laterra, John
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
KW - Cancer stem cell
KW - Differentiation
KW - Notch signaling
KW - Retinoic acid
KW - Transcription factor
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U2 - 10.1002/stem.561
DO - 10.1002/stem.561
M3 - Article
C2 - 21280156
AN - SCOPUS:79951836097
VL - 29
SP - 20
EP - 31
JO - STEM CELLS
JF - STEM CELLS
SN - 1066-5099
IS - 1
ER -