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Telomerase modulates Wnt signalling by association with target gene chromatin
Open accessAbstract
Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.
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“As expected, AAV9-mTERT-DN treatment increased CyclinD1 expression in a number of tissues (Fig 5A and B), in accordance with previous findings (Park et al, 2009).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Park et al, 2009
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“These results are consistent with previous findings that TERT can act as a transcriptional modulator not only in highly proliferating cells but also in terminally differentiated cells.16,27”
From TERT activation targets DNA methylation and multiple aging hallmarks (2024) · cites this paper as [27]
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“in agreement with the proposed role of TERT as activator of genes of the Wnt pathway (Park et al, 2009), tissues with increased TERT expression also showed increased expression of active β-catenin, as well as of its target gene cyclinD1, which in turn may mediate some of the known effects of TERT improving stem cell mobilization (Flores et al, 2005; Reya & Clevers, 2005; Sarin et al, 2005).”
From Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer (2012) · cites this paper as Park et al, 2009
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“Stable overexpression of TERT in mouse skin enhanced the ability of bulge stem cells to enter cell cycle when stimulated with phorbol esters (147).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [147]
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Citations
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“Remarkably and unexpectedly, a reverse transcriptase component (TERT) of telomerase has been shown to control Wnt signalling in development by binding to Wnt/catenin target gene chromatin [103].”
BackgroundhTERT-based therapy: A universal anticancer approach (Review)
Lü, M., Liao, Z., Zhao, X., FAN, Y.-H., Xian-long, L., Fang, D.-C., Guo, H. Y., & Yang, S. (2012) · Oncology Reports · doi:10.3892/or.2012.2036 · Cited by 47
“It has been reported that TERT controls stem cells via transcriptional regulation of a developmental program converging on the Wnt/ β -catenin signaling pathway (11).”
The Emerging Role of Telomerase Reverse Transcriptase in Mitochondrial DNA Metabolism
Gordon, D. M., & Santos, J. H. (2010) · Journal of Nucleic Acids · doi:10.4061/2010/390791 · Cited by 47
“For instance, TERT has been shown to play a role in chromatin remodeling and in DNA damage response and to act as a transcriptional modulator of the Wnt/betacatenin signaling pathways [4, 5].”
BackgroundHIV-1 Vpr Protein Inhibits Telomerase Activity via the EDD-DDB1-VPRBP E3 Ligase Complex
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Self-citationEmerging mechanisms of telomerase reactivation in cancer
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“This appears reasonable because Brg1 directly regulates Tcf2 expression (38, 39).”
BackgroundPES1 is a critical component of telomerase assembly and regulates cellular senescence
Cheng, L., Yuan, B., Ying, S., Niu, C., Mai, H.-X., Guan, X., Yang, X., Teng, Y., Lin, J., Huang, J., et al. (2019) · Science Advances · doi:10.1126/sciadv.aav1090 · Cited by 47
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BackgroundRecurrent epimutations activate gene body promoters in primary glioblastomaPreprint
Nagarajan, R. P., Zhang, B., Bell, R. J. A., Johnson, B., Olshen, A. B., Sundaram, V., Li, D., Graham, A. E., Diaz, A. A., Fouse, S. D., et al. (2014) · Genome Research · doi:10.1101/gr.164707.113 · Cited by 50
“Full-length TERT physically interacts with the SWI/SNF-related chromatin remodeling protein SMARCA4, and occupies and activates WNT-dependent genes, indicating a role in transcriptional activation (Park et al. 2009).”
BackgroundRegulation of telomerase activity by apparently opposing elements
Liu, J., Chen, S., Cong, Y.-S., Nicholls, C., Zhou, S.-F., Tao, Z., & Li, H. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.03.002 · Cited by 45
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Immortalized Muscle Cell Model to Test the Exon Skipping Efficacy for Duchenne Muscular Dystrophy
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“Telomerase has been proposed to have telomere-independent roles (independent of its catalytic activity) as a cofactor on the promoter of Wnt targeted genes [46], although questions have been raised about the relevance of this activation [42,47].”
BackgroundEl-Badawy, A., Ghoneim, N. I., Nasr, M. A., Elkhenany, H. A., Ahmed, T. A., Ahmed, S. M., & El‐Badri, N. (2018) · Biology Open · doi:10.1242/bio.034181 · Cited by 44
“Furthermore, the overexpression of hTERT in normal stem cells can enhance their mobilization and proliferation, which is achieved by activation of the canonical Wnt pathway (Park et al., 2009).”
Non-canonical roles of canonical telomere binding proteins in cancers
Akıncılar, S. C., Chan, C. H. T., Ng, Q. F., Fidan, K., & Tergaonkar, V. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03783-0 · Cited by 45
“On the other hand, in vivo studies revealed that overexpression of catalytically inactive TERT (DN-TERT) in the crypts of mouse intestines led to increased expression of a β-catenin driven gene, CD44, suggesting that reverse transcriptase activity is not required for TERT–TBE interaction [64].”
BackgroundInfluentialFleisig, H. B., Hukezalie, K. R., Thompson, C. A. H., Au‐Yeung, T., Ludlow, A. T., Zhao, C., & Wong, J. M. Y. (2015) · Oncogene · doi:10.1038/onc.2015.75 · Cited by 42
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“A recent report revealed that TERT interacts with BRG1 (Brahma-related gene 1, also called SMARCA4), a SWI/SNF (SWItch and Sucrose NonFermentable)-related chromatin remodeling protein, and directly activates Wnt-dependent signaling pathway [17,18].”
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“A number of studies have previously suggested that Brg1 facilitates trans-activation of Wnt target genes by activated bcatenin in cancer cell lines [12,13], zebrafish [31] and during mammalian vascular development [32].”
BackgroundInvolvement of Telomerase Reverse Transcriptase in Heterochromatin Maintenance
Maida, Y., Yasukawa, M., Okamoto, N., Ohka, S., Kinoshita, K., Totoki, Y., Ito, T. K., Minamino, T., Nakamura, H. K., Yamaguchi, S., et al. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00093-14 · Cited by 41
“In addition, several laboratories have demonstrated that TERT forms complexes independent of the telomerase RNA hTERC (9, 11, 15).”
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“…non-canonical functions interfering with extra-telomeric tumor-promoting pathways remains to be elucidated (Greider & Blackburn 1985, Cao et al. 2002, Stewart et al. 2002, Choi et al. 2008, Parkinson et al. 2008, Park et al. 2009, Martinez & Blasco 2011, Mukherjee et al. 2011, Liu et al. 2013b).”
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“Additionally, axis formation defects following TERT knockdown in Xenopus are consistent with a role for TERT in the Wnt pathway.(105) In contrast, in human cells, association of GNL3 with TERT-BRG1 produce RNA dependent RNA polymerase activity (RdRP), forming siRNA targeted to regulate centromeric alphoid domains, and…”
BackgroundInfluentialImplications of telomeres and telomerase in endometrial pathology
Hapangama, D. K., Kamal, A. M., & Saretzki, G. C. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmw044 · Cited by 46
“Telomerase may interact with various well-established proliferative pathways including EGFR signalling (Smith et al., 2003), MYC and Wnt/β-catenin pathways (Park et al., 2009; Hoffmeyer et al., 2012).”
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“A number of non-canonical functions for hTERT have been reported in literature, and the list is increasing rapidly [27,28,29,30,31,33,34,47,48,64].”
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Hippocampal TERT Regulates Spatial Memory Formation through Modulation of Neural Development
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“Moreover, it is found that TERT modulates Wnt/b-catenin signaling by association with the target gene chromatin (Park et al., 2009).”
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The Tumor Suppressor BCL7B Functions in the Wnt Signaling Pathway
Uehara, T., Kage-Nakadai, E., Yoshina, S., Imae, R., & Mitani, S. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004921 · Cited by 40
“In humans, BCL7B is a component of the SWI/SNF complex [66], which has multiple functions, including regulation of the Wnt pathway through transcriptional control of related signaling molecules [67].”
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Wnt Signaling in Adult Epithelial Stem Cells and Cancer
Tan, S. H., & Barker, N. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.11.017 · Cited by 42
Hexokinase 2 is a molecular bridge linking telomerase and autophagy
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Fisetin Promotes Hair Growth by Augmenting TERT Expression
Kubo, C., Ogawa, M., Uehara, N., & Katakura, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.566617 · Cited by 45
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The Role of Telomerase in Breast Cancer’s Response to Therapy
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“Thus, hTERT is involved in the regulation of gene expression, including cyclin D1, MYC, and AXIN2 [25,26].”
BackgroundChromatin remodeling and cancer: the critical influence of the SWI/SNF complex
Hao, F., Zhang, Y., Hou, J., & Zhao, B. (2025) · Epigenetics & Chromatin · doi:10.1186/s13072-025-00590-w · Cited by 47
“Telomerase directly regulates the Wnt/β-catenin signaling pathway by acting as a cofactor of the β-catenin transcriptional complex [29].”
Telomerase as a “stemness” enzyme
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Telomere-Regulating Genes and the Telomere Interactome in Familial Cancers
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“As previously discussed, TERT can also associate with SMARCA4, a member of the SWI/SNF chromatin-remodeling complex, and regulate Wnt-dependent promoters (84).”
BackgroundXie, L., Gazin, C., Park, S. M., Zhu, L. J., Debily, M.-A., Kittler, E. L. W., Zapp, M. L., Lapointe, D. S., Gobeil, S., Virbasius, C.-M. A., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1003151 · Cited by 41
“A variety of previous studies have shown that TERT can promote proliferation by multiple mechanisms, several of which are unrelated to telomere length including inhibiting apoptosis [50], regulating cell signaling pathways and/or stimulating expression of diverse growth-promoting genes (see, for example, [51–54]).”
BackgroundPan, Y., Meng, M., Zheng, N., Cao, Z., Yang, P., Xi, X., & Zhou, Q. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.11.024 · Cited by 41
“As a result, cells fail to complete senescence and turnover [25-27].”
BackgroundInfluentialWnt/β-Catenin Signaling Exacerbates Keloid Cell Proliferation by Regulating Telomerase
Yu, D., Shang, Y., Yuan, J., Ding, S., Luo, S., & Hao, L. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000447896 · Cited by 42
TERT, a promoter of CNS malignancies
Patel, B., Taiwo, R., Kim, A. H., & Dunn, G. P. (2020) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaa025 · Cited by 41
ZEB1 stimulates breast cancer growth by up-regulating hTERT expression
Pan, Y., Shen, X. H., Yang, W., Zhang, Y., Liu, C., & Huang, T. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.12.139 · Cited by 39
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Alcaraz‐Pérez, F., García‐Castillo, J., García‐Moreno, D., López‐Muñoz, A., Anchelin, M., Angosto-Bazarra, D., Zon, L. I., Mulero, V., & Cayuela, M. L. (2014) · Nature Communications · doi:10.1038/ncomms4228 · Cited by 41
TERT promoter mutations in thyroid cancer
Matsuse, M., & Mitsutake, N. (2023) · Endocrine Journal · doi:10.1507/endocrj.ej23-0136 · Cited by 40
Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1
Hong, J., Lee, J. H., & Chung, I. K. (2016) · Journal of Cell Science · doi:10.1242/jcs.181040 · Cited by 38
Self-citationHuman Telomerase RNA: Telomerase Component or More?
Rubtsova, M. P., & Донцова, О. А. (2020) · Biomolecules · doi:10.3390/biom10060873 · Cited by 38
“The activation of Wnt reporters by TERT in TERC-/- mouse embryonic fibroblasts was demonstrated previously [54].”
BackgroundBehrooz, A. B., & Syahir, A. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.642719 · Cited by 38
“Thus, the activated-TERT-Wnt/bcatenin axis might increase the proliferation of normal mouse stem cells (60, 69).”
BackgroundWnt Regulates TERT—Putting the Horse Before the Cart
Greider, C. W. (2012) · Science · doi:10.1126/science.1223785 · Cited by 38
Telomerase and its extracurricular activities
Jaiswal, R. K., Kumar, P., & Yadava, P. K. (2013) · Cellular & Molecular Biology Letters · doi:10.2478/s11658-013-0105-0 · Cited by 36
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“Evidence is emerging for a role of telomerase activity in stem cell biology that does not involve its role in telomere maintenance(51); for example, telomerase appears to modulate the Wnt–b-catenin signaling pathway in epidermal stem cells.(52) To date, virtually all studies on nontelomeric functions of telomerase hav…”
Hoffmann, J., & Spyridopoulos, I. (2011) · Future Cardiology · doi:10.2217/fca.11.55 · Cited by 36
“It is important to note, that human TERT catalytic subunit can also exert telomere-length independent roles, which include the regulation of stem cell function [53], transcriptional coactivation during Wnt signaling [54], and regulation of mitochondrial function [55].”
BackgroundBaruch-Eliyahu, N., Rud, V., Braiman, A., & Priel, E. (2019) · Scientific Reports · doi:10.1038/s41598-019-54741-7 · Cited by 37
Structures of telomerase subunits provide functional insights
Sekaran, V. G., Soares, J., & Jarstfer, M. B. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.07.019 · Cited by 36
Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential
Zehbe, I., Lichtig, H., Westerback, A., Lambert, P. F., Tommasino, M., & Sherman, L. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-77 · Cited by 36
“Differential binding to and altered expression of E6 targets involved in apoptosis [49] keratinocyte differentiation [32,33] and Wnt signaling [46,47,50] could be the reason for the observations described here.”
ResultTelomerase in Brain: The New Kid on the Block and Its Role in Neurodegenerative Diseases
Saretzki, G. C., & Wan, T. (2021) · Biomedicines · doi:10.3390/biomedicines9050490 · Cited by 38
“It can also interact with signalling pathways such as NF-KB, Myc and Wnt [17,18] as well as influence chromatin status [19].”
BackgroundGiunco, S., Celeghin, A., Gianesin, K., Dolcetti, R., Indraccolo, S., & Rossi, A. D. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.145 · Cited by 36
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“An important co-activator of -catenin is telomerase: the telomerase protein component TERT (telomerase reversed transcriptase) interacts with gene promoters of Wnt-dependent genes and activates their transcription (Park et al. 2009).”
BackgroundTelomerase and hallmarks of cancer: An intricate interplay governing cancer cell evolution
Kumar, N., & Sethi, G. (2023) · Cancer Letters · doi:10.1016/j.canlet.2023.216459 · Cited by 35
Riviere-Cazaux, C., Carlstrom, L. P., Neth, B. J., Olson, I., Rajani, K. R., Rahman, M., Ikram, S., Mansour, M. A., Mukherjee, B., Warrington, A. E., et al. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00476-8 · Cited by 38
Telomerase and Telomeres in Endometrial Cancer
Alnafakh, R., Adishesh, M., Button, L., Saretzki, G. C., & Hapangama, D. K. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00344 · Cited by 35
Ovarian Telomerase and Female Fertility
Toupance, S., Fattet, A.-J., Thornton, S. N., Bénétos, A., Guéant, J., & Koscinski, I. (2021) · Biomedicines · doi:10.3390/biomedicines9070842 · Cited by 36
“It was also shown that TERT could act as a transcriptional modulator of the Wnt/β-catenin signaling pathway [28] and stimulate β-catenin-mediated epithelial-mesenchymal transition [29].”
BackgroundMattiussi, M., Tilman, G., Lenglez, S., & Decottignies, A. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.11.004 · Cited by 37
A single-molecule assay for telomerase structure-function analysis
Wu, J. Y. J., Stone, M. D., & Zhuang, X. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1033 · Cited by 36
“protein can function in transcription regulation (31).”
R-spondin 1 promotes vibration-induced bone formation in mouse models of osteoporosis
Wang, H., Brennan, T. A., Russell, E., Kim, J., Egan, K. P., Chen, Q., Israelite, C. L., Schultz, D., Johnson, F. B., & Pignolo, R. J. (2013) · Journal of Molecular Medicine · doi:10.1007/s00109-013-1068-3 · Cited by 36
“, to physically occupy gene promoters of Wnt-dependent genes) and to thus serve as a transcriptional modulator of the Wnt signaling pathway [36].”
Telomere protein complexes and interactions with telomerase in telomere maintenance
Pinto, A. R. (2010) · Frontiers in bioscience · doi:10.2741/3683 · Cited by 36
“In human cancer and mouse ES cells, TERT forms a complex with BRG1 (Brahma-related gene 1 or called SMARCA4 (83).”
BackgroundInfluentialMicroenvironmental Regulation of Telomerase Isoforms in Human Embryonic Stem Cells
Radan, L., Hughes, C. S., Teichroeb, J. H., Zamora, F., Jewer, M., Postovit, L.-M. M., & Betts, D. H. (2014) · Stem Cells and Development · doi:10.1089/scd.2013.0373 · Cited by 34
“Full-length, constitutively spliced TERT modulates Wnt signaling without its telomeric ability [25].”
Eribulin Mesylate Targets Human Telomerase Reverse Transcriptase in Ovarian Cancer Cells
Yamaguchi, S., Maida, Y., Yasukawa, M., Kato, T., Yoshida, M., & Masutomi, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112438 · Cited by 33
“In addition, together with the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), TERT acts as a transcriptional modulator of the Wnt/b-catenin signaling pathway, contributing to self-renewal and proliferation during development [5].”
BackgroundComposition and Function of Telomerase—A Polymerase Associated with the Origin of Eukaryotes
Schrumpfová, P. P., & Fajkus, J. (2020) · Biomolecules · doi:10.3390/biom10101425 · Cited by 34
Wnt Signaling in the Tumor Microenvironment
Ruan, Y., Ogana, H. A. N., Gang, E., Kim, H. N., & Kim, Y. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-47189-7_7 · Cited by 35
“β-catenin directly augments TERT expression through promoter binding[21].”
BackgroundTelomeric impact of conventional chemotherapy
Lu, Y., Leong, W., Guérin, O., Gilson, É., & Ye, J. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0293-z · Cited by 32
“For example, it has been shown that the catalytic subunit of telomerase acts as a co-factor of the TCF ß-catenin complex involved in the activation of the canonical Wnt pathway through interaction with the chromatin-remodeling factor Brg1 [21].”
BackgroundWu, S., Ge, Y., Huang, L., Liu, H., Xue, Y., & Zhao, Y. B. (2014) · Cell Cycle · doi:10.4161/15384101.2014.946834 · Cited by 33
“Furthermore, TERT protein is thought to regulate Wnt signaling through binding to BRG1.(29) Additional experiments are needed to clarify whether and how BRG1 and b-catenin influence TERT expression.”
BackgroundInfluentialKotiyal, S., & Evason, K. J. (2021) · Cancers · doi:10.3390/cancers13164202 · Cited by 32
“This complex formation drives the expression of WNT target genes, such as C-MYC, EPCAM, CYCLIN D1, and CD44, which promote cell cycle progression, proliferation, metabolism, cell survival, immune tolerance, and angiogenesis [58,59].”
BackgroundInfluentialSfeir, A. J. (2012) · Journal of Cell Science · doi:10.1242/jcs.106831 · Cited by 32
“Telomerase research has moved into extra dimensions in recent years, as the enzyme has been found to modulate the Wnt signaling pathways (Park et al., 2009), display an RNA-dependent RNA polymerase activity (Maida et al.”
BackgroundStructure–function relationship and biogenesis regulation of the human telomerase holoenzyme
Hukezalie, K. R., & Wong, J. M. Y. (2013) · FEBS Journal · doi:10.1111/febs.12272 · Cited by 32
Padhi, S., Saha, A., Kar, M., Ghosh, C., Adhya, A. K., Baisakh, M. R., Mohapatra, N., Venkatesan, S., Hande, M. P., & Banerjee, B. (2015) · Journal of Cancer · doi:10.7150/jca.9558 · Cited by 31
“[29] Mutations in β-catenin results in upregulation of hTert expression facilitating stabilization of the telomeres thus providing a significant hall mark for tumorigenesis.”
Ameri, Z., Ghiasi, S., Farsinejad, A., Hassanshahi, G., Ehsan, M., & Fatemi, A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.04.060 · Cited by 32
Protsenko, E., Rehkopf, D. H., Prather, A. A., Epel, E. S., & Lin, J. (2020) · PLoS ONE · doi:10.1371/journal.pone.0240185 · Cited by 29
“For example, in addition to extending telomeres, telomerase protein gene hTERT is also reported to be involved in NF-kb and Wnt/b-catenin transcriptional pathways [63, 64] and is localized to mitochondria to inhibit caspase mediated apoptosis [65, 66].”
BackgroundWNT Signalling in Lung Physiology and Pathology
Hu, Y., Ciminieri, C., Hu, Q., Lehmann, M., Königshoff, M., & Gosens, R. (2021) · Handbook of experimental pharmacology · doi:10.1007/164_2021_521 · Cited by 31
Fatemi, A., Safa, M., & Kazemi, A. (2015) · Tumor Biology · doi:10.1007/s13277-015-3575-z · Cited by 32
“These activities included regulation of cell cycle and gene expression [12–15], inhibition of apoptosis [16–18], and modulation of cellular signaling such as NF-κB [19, 20].”
BackgroundJaitner, S., Reiche, J. A., Schäffauer, A. J., Hiendlmeyer, E., Herbst, H., Brabletz, T., Kirchner, T., & Jung, A. (2012) · Cell Cycle · doi:10.4161/cc.21790 · Cited by 32
Liu, C. C., Ma, D., Yan, T., Fan, X., Poon, Z., Poon, L.-F., Goh, S.-A., Rozen, S., Hwang, W. Y. K., Tergaonkar, V., et al. (2016) · Stem Cells · doi:10.1002/stem.2431 · Cited by 29
Lineage plasticity and histological transformation: tumor histology as a spectrum
Li, X., Gardner, E. E., Molina‐Pinelo, S., Wilhelm, C., Mu, P., & Quintanal-Villalonga, À. (2025) · Cell Research · doi:10.1038/s41422-025-01180-x · Cited by 33
Epithelial stem cells: An epigenetic and wnt‐centric perspective
Gu, B., Watanabe, K., & Dai, X. (2010) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22650 · Cited by 32
“Further strengthening this link is the recent finding that b-catenin converges with telomerase, another central regulator of stem cell maintenance and activation, on interaction with BRG1 and activation of downstream target genes [Park et al., 2009].”
BackgroundYang, T.-L. B., Chen, Q., Deng, J. T., Jagannathan, G., Tobias, J. W., Schultz, D., Wang, S., Lengner, C. J., Rustgi, A. K., Lynch, J. P., et al. (2017) · Nature Communications · doi:10.1038/ncomms14766 · Cited by 31
“These findings reveal a positive feedback loop between telomere capping and Wnt pathway activity, and are distinct from previous suggestions of connections between Wnt and the catalytic subunit of telomerase, TERT (refs 15–17).”
The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development
Tornesello, M. L., Cerasuolo, A., Starita, N., Tornesello, A. L., Bonelli, P., Tuccillo, F. M., Buonaguro, L., Isaguliants, M. G., & Buonaguro, F. M. (2022) · Cancers · doi:10.3390/cancers14215257 · Cited by 29
Multiple Actions of Telomerase Reverse Transcriptase in Cell Death Regulation
Palamarchuk, A. I., Kovalenko, E. I., & Streltsova, M. A. (2023) · Biomedicines · doi:10.3390/biomedicines11041091 · Cited by 31
“It became evident that TERT is involved in the regulation of various signal transduction pathways and even in gene expression [32,40,41].”
BackgroundInfluentialhTERT promoter activity identifies osteosarcoma cells with increased EMT characteristics
Yu, L., Liu, S., Guo, W., Zhang, C., Zhang, B., Yan, H., & Wu, Z. (2013) · Oncology Letters · doi:10.3892/ol.2013.1692 · Cited by 31
“Furthermore, overexpression of hTERT in normal stem cells may enhance their mobilization and proliferation, which is achieved by activation of the canonical wnt pathway (31).”
Liu, T., Yu, H., Ding, L., Wu, Z. B., Santos, F. G. D. L., Liu, J., Ullenbruch, M. R., Hu, B., Martins, V., & Phan, S. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142547 · Cited by 33
“Moreover, in addition to this canonical telomere maintenance function, there is mounting evidence that TERT has non-canonical functions of potential import in development, cell differentiation and certain disease processes [14, 15].”
BackgroundTERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary Thyroid Carcinoma
Oh, E. J., Lee, S., Bae, J. S., Kim, Y., Jeon, S., & Jung, C. K. (2016) · Endocrine Pathology · doi:10.1007/s12022-016-9454-3 · Cited by 30
Dzobo, K., Thomford, N. E., & Senthebane, D. A. (2019) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2019.0147 · Cited by 29
“Thus, Wnt/ b -catenin signaling was associated with telomerase activity (Park et al., 2009).”
Cobrinik, D. E., Ostrovnaya, I., Hassimi, M., Tickoo, S. K., Cheung, I. Y., & Cheung, N. V. (2013) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22110 · Cited by 29
“In addition to maintaining telomeres, TERT overexpression promotes Wnt signaling, DNAdamage repair, cell proliferation and survival (Kang et al., 2004; Masutomi et al., 2005; Park et al., 2009; Mukherjee et al., 2011; Fleisig and Wong, 2012), genomic instability (Zhou et al.”
BackgroundTelomerase Reverse Transcriptase Regulates microRNAs
Lassmann, T., Maida, Y., Tomaru, Y., Yasukawa, M., Ando, Y., Kojima, M., Kasim, V., Simon, C., Daub, C. O., Carninci, P., et al. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms16011192 · Cited by 27
“Recently, we and others have found that TERT interacts with BRG1 and NS and forms the complexes that regulate gene transcription and stem cell functions in both normal and malignant cells [21,25].”
Background
Metadata
- Authors
- Park, J.-I., Venteicher, A. S., Hong, J. Y., Choi, J., Jun, S., Shkreli, M., Chang, W., Meng, Z., Cheung, P., Ji, H., McLaughlin, M., Veenstra, T. D., Nusse, R., McCrea, P. D., & Artandi, S. E.
- Affiliations
- Stanford Medicine (US)
- The University of Texas MD Anderson Cancer Center (US)
- National Cancer Institute (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Artandi, Steven E.
- ORCID
- Venue
- Nature
- Published
- 2009-07
- Volume
- 460
- Issue
- 7251
- Pages
- 66-72
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4349391
- OpenAlex
- W2086316954
- Cited by
- 707
- References
- 51
- Citations by year
- 2026: 17 · 2025: 28 · 2024: 23 · 2023: 41 · 2022: 32 · 2021: 48 · 2020: 48 · 2019: 34 · 2018: 38 · 2017: 29 · 2016: 43 · 2015: 48 · 2014: 58 · 2013: 58 · 2012: 60
- FWCI
- 21.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DigitalCommons-Cedarville (Cedarville University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Cancer Institute (CA111691, R01CA125453, CA125453, R01CA111691, P30CA124435)
- National Institute of General Medical Sciences (R01GM052112)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- telomerase, telomerase reverse transcriptase, Wnt/β-catenin signaling, SMARCA4, chromatin remodeling, transcriptional regulation, epidermal stem cells, stem cell self-renewal, carcinogenesis, anterior-posterior axis, homeotic transformation, promoter, SWI/SNF complex
- MeSH terms
- Animals, Cell Line, Choristoma, Chromatin, DNA Helicases, HeLa Cells, Humans, Intestine, Small, Nuclear Proteins, Oocytes, Plasmids, Promoter Regions, Genetic, Transcription Factors, Xenopus laevis, Signal Transduction, Genes, Reporter, Telomerase, Somites, Wnt Proteins, beta Catenin, Mice, Wnt3 Protein
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