Krüppel-Like Transcription Factor 4 Contributes to Maintenance of Telomerase Activity in Stem Cells§

Authors

  • Chui-Wei Wong,

    1. Departments of Microbiology andNational Taiwan University, Taipei, Taiwan
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  • Pei-Shan Hou,

    1. Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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    • 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.

  • Shun-Fu Tseng,

    1. Departments of Microbiology andNational Taiwan University, Taipei, Taiwan
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    • 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.

  • Chung-Liang Chien,

    1. Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
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    • 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.

  • Kou-Juey Wu,

    1. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan
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    • 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.

  • Hsin-Fu Chen,

    1. Department of Obstetrics and Gynecology andKanazawa University, School of Medicine, Kanazawa, Japan
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    • 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.

  • Hong-Nerng Ho,

    1. Department of Obstetrics and Gynecology andKanazawa University, School of Medicine, Kanazawa, Japan
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    • 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.

  • Satoru Kyo,

    1. Department of Obstetrics and Gynecology, Kanazawa University, School of Medicine, Kanazawa, Japan
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    • 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.

  • Shu-Chun Teng

    Corresponding author
    1. Departments of Microbiology andNational Taiwan University, Taipei, Taiwan
    2. Institute of Internal Medicine, National Taiwan University Hospital, Taipei, 10018, Taiwan
    • Department of Microbiology, College of Medicine, National Taiwan University, No. One, Sec. One, Jen-Ai Road, Taipei, 10051, Taiwan
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    • 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.

    • Telephone: 886-2-23123456 (ext. 88294); Fax: 886-2-23915293


  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLS EXPRESS July 13, 2010.

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. STEM Cells 2010; 28:1510–1517.

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