Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.
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.
Department of Molecular Embryology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Katrin
K
Hoffmeyer
Angelo
A
Raggioli
Stefan
S
Rudloff
Roman
R
Anton
Andreas
A
Hierholzer
Ignacio
I
Del Valle
Kerstin
K
Hein
Riana
R
Vogt
Rolf
R
Kemler
D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure; D059505:Telomere Homeostasis; D024363:Transcription Initiation Site; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; D051153:Wnt Proteins; D051176:beta Catenin; D019098:Telomerase; C509187:Tert protein, mouse