Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells

Science. 2012 Jun 22;336(6088):1549-54. doi: 10.1126/science.1218370.

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(ΔEx3/+)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / metabolism*
  • Animals
  • Cell Line, Tumor
  • Embryonic Stem Cells / metabolism*
  • HEK293 Cells
  • Humans
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Telomerase / genetics*
  • Telomerase / metabolism
  • Telomere / metabolism
  • Telomere / ultrastructure
  • Telomere Homeostasis
  • Transcription Initiation Site
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • GKLF protein
  • Kruppel-Like Transcription Factors
  • RNA, Messenger
  • Wnt Proteins
  • beta Catenin
  • Telomerase
  • Tert protein, mouse