Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells

Chui Wei Wong, Pei Shan Hou, Shun Fu Tseng, Chung Liang Chien, Kou Juey Wu, Hsin Fu Chen, Hong Nerng Ho, Satoru Kyo, Shu Chun Teng

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Abstract

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.

Original languageEnglish
Pages (from-to)1510-1517
Number of pages8
JournalStem Cells
Volume28
Issue number9
DOIs
Publication statusPublished - Sep 1 2010
Externally publishedYes

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Keywords

  • KLF4
  • Stem cells
  • Telomerase
  • TERT
  • Transcriptional activation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Wong, C. W., Hou, P. S., Tseng, S. F., Chien, C. L., Wu, K. J., Chen, H. F., Ho, H. N., Kyo, S., & Teng, S. C. (2010). Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells. Stem Cells, 28(9), 1510-1517. https://doi.org/10.1002/stem.477