Wnt/β-Catenin Signaling Regulates Telomerase in Stem Cells and Cancer Cells

Katrin Hoffmeyer, Angelo Raggioli, Stefan Rudloff, Roman Anton,^* Andreas Hierholzer, Ignacio Del Valle, Kerstin Hein, Riana Vogt, Rolf Kemler

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^Ex3/+) 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.

Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, D-79108 Freiburg, Germany.

To whom correspondence should be addressed. E-mail: kemler{at}immunbio.mpg.de

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