The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer
Open accessAbstract
Telomerase activation plays a critical role in human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear. The human telomerase reverse transcriptase (hTERT) promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. Deregulation of the Wnt/β-catenin signaling pathway is reported to be associated with human carcinogenesis. However, little is known about whether the Wnt/β-catenin pathway is involved in activating hTERT transcription and inducing telomerase activity (TA). In this study, we report that hTERT is a novel target of the Wnt/β-catenin pathway. Transient activation of the Wnt/β-catenin pathway either by transfection of a constitutively active form of β-catenin or by LiCl or Wnt-3a conditioned medium treatment induced hTERT mRNA expression and elevated TA in different cell lines. Furthermore, we found that silencing endogenous β-catenin expression by β-catenin gene-specific shRNA effectively decreased hTERT expression, suppressed TA, and accelerated telomere shortening. Of the four members of the lymphoid-enhancing factor (LEF)/T-cell factor (TCF) family, only TCF4 showed more effective stimulation on the hTERT promoter. Ectopic expression of a dominant negative form of TCF4 inhibited hTERT expression in cancer cells. Through promoter mapping, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we found that hTERT is a direct target of β-catenin·TCF4-mediated transcription and that the TCF4 binding site at the hTERT promoter is critical for β-catenin·TCF4-dependent expression regulation. Given the pivotal role of telomerase in carcinogenesis, these results may offer insight into the regulation of telomerase in human cancer.
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Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 3×
“A high level of telomerase activity (TA)(2) is detected in about 90% of human cancer specimens, whereas most somatic cells do not display TA or express it only at very low levels in a cell cycle-dependent manner (5, 6).”
BackgroundMethodInfluentialExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05245.x · Cited by 2,096 · cited 1×
“Human somatic cells gradually lose telomeric sequences as a result of incomplete replication (45).”
BackgroundA telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis
Greider, C. W., & Blackburn, E. H. (1989) · Nature · doi:10.1038/337331a0 · Cited by 1,643 · cited 1×
“Telomerase is a ribonucleoprotein that catalyzes de novo synthesis of repetitive telomeric DNA after cell division and maintains chromosomal stability, leading to cellular immortalization (2, 3).”
BackgroundLithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells
Stambolic, V., Ruel, L., & Woodgett, J. R. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70790-2 · Cited by 1,321
Telomerase modulates Wnt signalling by association with target gene chromatin
Park, J.-I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., et al. (2009) · Nature · doi:10.1038/nature08137 · Cited by 707 · cited 2×
“(51) showed that hTERT plays an essential role in the Wnt/ -catenin signaling pathway by serving as a cofactor in a -catenin transcriptional complex.”
BackgroundTelomerase, Cell Immortality, and Cancer
Harley, C. B., Kim, N. W., Prowse, K. R., Weinrich, S. L., Hirsch, K. S., West, M. D., Bacchetti, S., Hirte, H. W., Counter, C. M., Greider, C. W., et al. (1994) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1994.059.01.035 · Cited by 396
Apc modulates embryonic stem-cell differentiation by controlling the dosage of β-catenin signaling
Kielman, M. F., Rindapää, M., Gaspar, C., van Poppel, N., Breukel, C., van Leeuwen, S., Taketo, M. M., Roberts, S., Smits, R., & Fodde, R. (2002) · Nature Genetics · doi:10.1038/ng1045 · Cited by 362
Targeting telomerase for cancer therapeutics
Shay, J. W., & Keith, W. N. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604209 · Cited by 171
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Cited by
The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids
Kessler, M., Hoffmann, K., Brinkmann, V., Thieck, O., Jackisch, S., Toelle, B., Berger, H., Mollenkopf, H.-J., Mangler, M., Sehouli, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms9989 · Cited by 459
Long-term lithium treatment in bipolar disorder is associated with longer leukocyte telomeres
Martinsson, L., Wei, Y., Xu, D., Melas, P. A., Mathé, A. A., Schalling, M., Lavebratt, C., & Backlund, L. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.37 · Cited by 179
Telomeres and telomerase in oncogenesis (Review)
Trybek, T., Kowalik, A., Góźdź, S., & Kowalska, A. (2020) · Oncology Letters · doi:10.3892/ol.2020.11659 · Cited by 119
Wang, Y., Chen, S., Yan, Z., & Pei, M. (2019) · Cell & Bioscience · doi:10.1186/s13578-018-0264-9 · Cited by 56
Metadata
- Authors
- Zhang, Y., Toh, L., Lau, P., & Wang, X.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 287
- Issue
- 39
- Pages
- 32494-32511
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2138171776
- Cited by
- 180
- References
- 12
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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