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Science. 2012 Jun 22;336(6088):1549-54. doi: 10.1126/science.1218370.

Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.

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  • 1Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

Abstract

Telomerase activity controls telomere length and plays a pivotal role in stem cells, aging, and cancer. Here, we report a molecular link between Wnt/β-catenin signaling and the expression of the telomerase subunit Tert. β-Catenin-deficient mouse embryonic stem (ES) cells have short telomeres; conversely, ES cell expressing an activated form of β-catenin (β-cat(ΔEx3/+)) have long telomeres. We show that β-catenin regulates Tert expression through the interaction with Klf4, a core component of the pluripotency transcriptional network. β-Catenin binds to the Tert promoter in a mouse intestinal tumor model and in human carcinoma cells. We uncover a previously unknown link between the stem cell and oncogenic potential whereby β-catenin regulates Tert expression, and thereby telomere length, which could be critical in human regenerative therapy and cancer.

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PMID:
22723415
[PubMed - indexed for MEDLINE]
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