Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells
Journal
Stem Cells
Journal Volume
28
Journal Issue
9
Pages
1510-1517
Date Issued
2010
Author(s)
Wong C.-W.
Hou P.-S.
Tseng S.-F.
Wu K.-J.
HSIN-FU CHEN
Kyo S.
Abstract
The zinc finger Kr?ppel-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. ? AlphaMed Press.
SDGs
Other Subjects
kruppel like factor 4; luciferase; telomerase; telomerase reverse transcriptase; kruppel like factor; kruppel like factor 4; telomerase; TERT protein, human; animal cell; article; binding site; carcinogenesis; cell proliferation; cell renewal; chromatin immunoprecipitation; embryo; embryonic stem cell; enzyme activity; enzyme regulation; fibroblast; gel mobility shift assay; gene expression regulation; human; human cell; immunocytochemistry; nonhuman; promoter region; protein function; stem cell; telomere; Western blotting; animal; cell line; enzyme activation; enzymology; genetic transfection; genetics; metabolism; mouse; pathology; RNA interference; squamous cell carcinoma; transcription initiation; two hybrid system; Animals; Binding Sites; Carcinoma, Squamous Cell; Cell Line; Cell Proliferation; Embryonic Stem Cells; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kruppel-Like Transcription Factors; Mice; Promoter Regions, Genetic; RNA Interference; Telomerase; Transcriptional Activation; Transfection; Two-Hybrid System Techniques; Animals; Binding Sites; Carcinoma, Squamous Cell; Cell Line; Cell Proliferation; Embryonic Stem Cells; Enzyme Activation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kruppel-Like Transcription Factors; Mice; Promoter Regions, Genetic; RNA Interference; Telomerase; Transcriptional Activation; Transfection; Two-Hybrid System Techniques
Type
journal article