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EMBO Rep. 2013 Apr;14(4):356-63. doi: 10.1038/embor.2013.16. Epub 2013 Feb 22.

Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway.

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1
Faculté de Médecine de Nice, Institut for Research on Cancer and Aging, Nice (IRCAN), Nice University, Nice, France.

Abstract

The DNA-binding protein TRF2 is essential for telomere protection and chromosome stability in mammals. We show here that TRF2 expression is activated by the Wnt/β-catenin signalling pathway in human cancer and normal cells as well as in mouse intestinal tissues. Furthermore, β-catenin binds to TRF2 gene regulatory regions that are functional in a luciferase transactivating assay. Reduced β-catenin expression in cancer cells triggers a marked increase in telomere dysfunction, which can be reversed by TRF2 overexpression. We conclude that the Wnt/β-catenin signalling pathway maintains a level of TRF2 critical for telomere protection. This is expected to have an important role during development, adult stem cell function and oncogenesis.

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PMID:
23429341
PMCID:
PMC3615653
DOI:
10.1038/embor.2013.16
[Indexed for MEDLINE]
Free PMC Article
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