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Updated: Jun 11, 2026

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells
Chui-Wei Wong1, Pei-Shan Hou, Shun-Fu Tseng
1Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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.
Insights
Krüppel-like factor 4 (KLF4) regulates human telomerase reverse transcriptase (hTERT) expression, impacting cancer and stem cell proliferation. KLF4 activates hTERT in some cells while its reduction lowers hTERT in cancer cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- Krüppel-like factor 4 (KLF4) is involved in cancer and stem cell regulation.
- KLF4's precise roles and targets in these processes remain unclear.
Purpose of the Study:
- To investigate the link between KLF4 and telomerase regulation.
- To elucidate KLF4's contribution to cancer formation and stem cell maintenance.
Main Methods:
- Analysis of KLF4's effect on human telomerase reverse transcriptase (hTERT) expression.
- Identification of KLF4 binding sites in the hTERT promoter.
- Examination of KLF4 and hTERT interplay in various cell types, including human embryonic stem cells.
Main Results:
- KLF4 activates hTERT expression in telomerase-low ALT and fibroblast cells.
- Downregulation of KLF4 reduces hTERT expression in cancer and stem cells.
- KLF4 binds to the hTERT promoter, mediating hTERT induction.
- hTERT expression compensates for KLF4 in maintaining human embryonic stem cell self-renewal.
Conclusions:
- hTERT is a key target of KLF4 in cancer and stem cells.
- KLF4-mediated hTERT regulation is crucial for long-term cellular proliferation potential.
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