Stem cells, similarly to cancer cells, possess long telomeres. Although telomerase (TERT) is known to control telomere length, the mechanisms regulating its expression have not been fully elucidated. Kemler and colleagues reveal that the Wnt–β-catenin pathway — which regulates pluripotency in stem cells and is commonly dysregulated in cancers — directly promotes TERT expression in both of these biological contexts (Science 336, 1549–1554; 2012).

The authors found that β-catenin activity directly correlated with Tert expression in mouse embryonic stem cells. Chromatin immunoprecipitation assays revealed that β-catenin bound to the Tert promoter and recruited chromatin remodelling factors and active RNA polymerase II. Wnt3a enhanced this interaction. Interestingly, the transcription factor Klf4, which regulates both pluripotency and tumorigenesis, was necessary for efficient β-catenin accumulation at the Tert promoter. β-catenin was also identified at the Tert promoter in adult intestinal stem cells and primary neurospheres.

In a mouse model of β-catenin-driven intestinal hyperplasia, β-catenin was shown to accumulate at the Tert promoter, along with RNA Pol II. This accumulation was also seen in human embryonal carcinoma and colorectal carcinoma cell lines. However, β-catenin depletion decreased hTERT levels in these cells. These results offer direct evidence that β-catenin promotes TERT expression in stem and cancer cells, revealing an intriguing mechanistic link between tumorigenesis and pluripotency.