Author contributions: C.-W.W.: conception and design, collection and/or assembly of data, data analysis and interpretation; P.-S.H.: collection and/or assembly of data; S.-F.T.: collection and/or assembly of data; C.-L.C.: provision of study material or patients; K.-J.W.: data analysis and interpretation; H.-F.C.: provision of study material or patients; H.-N.H.: provision of study material or patients; S.K.: provision of study material or patients; S.-C.T.: conception and design, data analysis and interpretation, manuscript writing.
Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 13 JUL 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 9, pages 1510–1517, September 2010
How to Cite
Wong, C.-W., Hou, P.-S., Tseng, S.-F., Chien, C.-L., Wu, K.-J., Chen, H.-F., Ho, H.-N., Kyo, S. and Teng, S.-C. (2010), Krüppel-Like Transcription Factor 4 Contributes to Maintenance of Telomerase Activity in Stem Cells. STEM CELLS, 28: 1510–1517. doi: 10.1002/stem.477
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS July 13, 2010.
- Issue published online: 13 JUL 2010
- Article first published online: 13 JUL 2010
- Manuscript Accepted: 30 JUN 2010
- Manuscript Received: 20 JAN 2010
- National Science Council. Grant Number: NRPGM-98-3112-B-002-039
- National Health Research Institute of Taiwan. Grant Number: NHRI-EX98-9727BI
- Stem cells;
- Transcriptional activation
The zinc finger Krüppel-like transcription factor 4 (KLF4) has been implicated in cancer formation and stem cell regulation. However, the function of KLF4 in tumorigenesis and stem cell regulation are poorly understood due to limited knowledge of its targets in these cells. In this study, we have revealed a surprising link between KLF4 and regulation of telomerase that offers important insight into how KLF4 contributes to cancer formation and stem cell regulation. KLF4 sufficiently activated expression of the human telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT), in telomerase-low alternative lengthening of telomeres (ALT), and fibroblast cells, while downregulation of KLF4 reduced its expression in cancerous and stem cells, which normally exhibits high expression. Furthermore, KLF4-dependent induction of hTERT was mediated by a KLF4 binding site in the proximal promoter region of hTERT. In human embryonic stem cells, expression of hTERT replaced KLF4 function to maintain their self-renewal. Therefore, our findings demonstrate that hTERT is one of the major targets of KLF4 in cancer and stem cells to maintain long-term proliferation potential. STEM Cells 2010; 28:1510–1517.