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

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.
Authors	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
Journal	Stem cells (Dayton, Ohio) (Stem Cells) Vol. 28 Issue 9 Pg. 1510-7 (Sep 2010) ISSN: 1549-4918 [Electronic] England
PMID	20629177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	KLF4 protein, human Klf4 protein, mouse Kruppel-Like Factor 4 Kruppel-Like Transcription Factors TERT protein, human Telomerase
Topics	Animals Binding Sites Carcinoma, Squamous Cell (enzymology, pathology) Cell Line Cell Proliferation Embryonic Stem Cells (enzymology) Enzyme Activation Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Kruppel-Like Factor 4 Kruppel-Like Transcription Factors (genetics, metabolism) Mice Promoter Regions, Genetic RNA Interference Telomerase (genetics, metabolism) Transcriptional Activation Transfection Two-Hybrid System Techniques

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