β-Catenin Regulates Telomerase in Stem and Cancer Cells

High telomerase activity is important for stem cells, aging, andcancer. Here, we report a molecular link between β-catenin andthe expression of the telomerase subunit Tert. β-Catenin deficient(β-cat-/-) embryonic stem (ES) cells have short telomeres;conversely ES cell expressing an activated form of β-catenin(β-catΔEx۳/+) have long telomeres. β-Catenin regulates Tert expressionthrough the interaction with Klf۴, a core component ofthe pluripotency transcriptional network. Binding of β-cateninto the Tert promoter is a general mechanism occurring in adultstem cells, in a mouse intestinal tumour model, and in humancarcinoma cells. We uncover a novel link between the stem celland oncogenic potential with β-catenin regulating Tert expressionand, thereby, telomere length, which could be of criticalimportance in human regenerative therapy and cancer.