Research Article

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

Science  22 Jun 2012:
Vol. 336, Issue 6088, pp. 1549-1554
DOI: 10.1126/science.1218370

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From Wnt Signals to Telomerase Activity

Telomerase activity is associated with stem cell renewal and cancers, whereas a decrease in telomerase activity is seen during cell differentiation and senescence. Wnt/β-catenin signaling is also a critical regulator of stem cells, and deregulation of the pathway is associated with cancer. Now, Hoffmeyer et al. (p. 1549; see the Perspective by Greider) have found a link between these two pathways. In embryonic stem cells, β-catenin was able to regulate telomerase expression and activity directly. Similar observations were obtained in adult stem cells, a model of intestinal tumors, and human cancer cells.

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-catΔEx3/+) 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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