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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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Items 401–500 of 710
Chen, S., Yang, L., Dong, H. F., & Guo, H. Y. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108700 · Cited by 15
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BackgroundExercise, telomerase activity, and cardiovascular disease prevention
Stellos, K., & Spyridopoulos, I. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy707 · Cited by 18
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Genotoxic Stress, DNA Repair, and Crop Productivity
Balestrazzi, A., Macovei, A., Donà, M., Carbonera, D., & Confalonieri, M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4633-0_7 · Cited by 15
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Telomerase is required for glomerular renewal in kidneys of adult mice
Montandon, M., Hamidouche, T., Yart, L., Duret, L. C., Pons, C., Soubeiran, N., Pousse, M., Cervera, L., Vial, V., Fassy, J., et al. (2022) · npj Regenerative Medicine · doi:10.1038/s41536-022-00212-z · Cited by 16
Self-citationQin, Y., Guo, H. Y., Tang, B., & Yang, S. (2014) · International Journal of Oncology · doi:10.3892/ijo.2014.2470 · Cited by 15
PINX1 and TERT Are Required for TNF-α–Induced Airway Smooth Muscle Chemokine Gene Expression
Deacon, K., & Knox, A. J. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1700414 · Cited by 15
“Recent studies have shown that TERT is required for the activity of the transcription factors with roles in chemokine expression and inflammation: Myc (11), TCF/LEF (12), and, particularly, NF-kB (13).”
BackgroundWhen the Ends Are Really the Beginnings: Targeting Telomerase for Treatment of GBM
Bollam, S., Berens, M. E., & Dhruv, H. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0825-7 · Cited by 14
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Ma, Z.-X., Yang, C., Li, M., & Tu, H. (2019) · Hepatoma Research · doi:10.20517/2394-5079.2018.104 · Cited by 15
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Barbaric, I., & Harrison, N. J. (2012) · The International Journal of Developmental Biology · doi:10.1387/ijdb.123503ib · Cited by 13
“That TERT has previously been shown to modulate the Wnt pathway (Park et al., 2009) demonstrates cross-talk between these pathways, though the work described here was the first time that this relationship had been investigated in ES cells.”
BackgroundBou‐Rouphael, J., & Durand, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.784998 · Cited by 13
“Notably, the ability of both normal and CSCs to maintain long telomeres – an important feature to prevent their cellular aging – appears to be under direct transcriptional control of β-catenin-TCF/LEF (Park et al., 2009; Noureen et al., 2021).”
BackgroundNovo, C. L., & Londoño‐Vallejo, A. (2012) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2012.02.001 · Cited by 14
Tumor viruses and replicative immortality – Avoiding the telomere hurdle
Chen, X., Kamranvar, S. A., & Masucci, M. G. (2014) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.01.006 · Cited by 14
Rhee, J., Park, K., Kim, K. C., Shin, C. Y., & Chung, C. (2018) · Europe PMC (PubMed Central) · doi:10.14348/molcells.2018.0145 · Cited by 14
“…gene expression, potentially exerting such regulatory effects on both Pax6 expression (Eberhardt et al., 2006; Matsumoto et al., 2006) and Wnt-signaling (Choi et al., 2008; Park et al., 2009; Zhao et al., 2010), indicating that changes in TERT levels may underlie neurodevelopmental defects.”
BackgroundBoscolo‐Rizzo, P., Rampazzo, E., Polesel, J., Giunco, S., Menegaldo, A., Mantovani, M., Stellin, M., Bandolin, L., Spinato, G., Mistro, A. D., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-54028-x · Cited by 13
Durak-Kozica, M., Paszek, E., & Stępień, E. Ł. (2019) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2019.8 · Cited by 13
Ding, X., Nie, Z., She, Z., Bai, X., Yang, Q., Wang, F., Wang, F., & Geng, X. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6636510 · Cited by 13
Giunco, S., Boscolo‐Rizzo, P., Rampazzo, E., Tirelli, G., Alessandrini, L., Carlo, R. D., Rossi, M., Nicolai, P., Menegaldo, A., Carraro, V., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.782658 · Cited by 14
González‐Moles, M. Á., Moya-González, E., García-Ferrera, A., Nieto-Casado, P., & Ramos‐García, P. (2022) · Cancers · doi:10.3390/cancers14153673 · Cited by 13
“Some of these noncanonical functions seem to be achieved by the ability of TERT to act as a transcriptional cofactor in the WNT/β-catenin pathway [22,69,70] and as a cofactor of NF-kβ, thus contributing to the regulation of the target genes of this transcription factor and as a modulator of MYCdependent transcriptiona…”
BackgroundFernandez, R. J., & Johnson, F. B. (2018) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13692 · Cited by 12
TERT Promoter Mutations Increase Sense and Antisense Transcription from the TERT Promoter
Hafezi, F., Jaxel, L., Lemaire, M., Turner, J. D., & Perez-Bercoff, D. (2021) · Biomedicines · doi:10.3390/biomedicines9121773 · Cited by 14
“It contributes to cell survival and proliferation by facilitating Wnt/β-catenin-dependent [93,94], c-Mycdependent [95,96], and NF-κB-dependent gene transcription [97,98], thereby sustaining both oncogenic signaling pathways and its own transcription in a feedforward loop [99,100].”
BackgroundAmin, A., Morello, M., Petrara, M. R., Rizzo, B., Argenton, F., Rossi, A. D., & Giunco, S. (2023) · Cancers · doi:10.3390/cancers15102673 · Cited by 13
“TERT’s involvement in the regulation of WNT/β-catenin has been extensively documented [30,32,33,67,68]; thus, the possibility that MYC transcriptional downregulation following TERT inhibition could be mediated via WNT/β-catenin was investigated by evaluating the transcriptional levels of β-catenin (CTNNB1) and the WNT…”
BackgroundInfluentialTeng, Y., Huang, D. Q., Li, R. X., Yi, C., & Zhan, Y. (2023) · World Journal of Oncology · doi:10.14740/wjon1624 · Cited by 12
Terra, M. L., Sant’Anna, T. B. F., de Barros, J. J. F., & Araujo, N. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072889 · Cited by 13
“Some studies suggest that β -catenin transcriptional activity may directly or indirectly influence TERT expression, further reinforcing the interplay between these pathways in tumor development [36,37,129].”
Hartwig, F. P., & Collares, T. V. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.03.003 · Cited by 11
Deng, W., Jiao, N., Li, N., Wan, X., Luo, S., & Zhang, Y. (2015) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2015.04.011 · Cited by 12
The Telomerase Connection of the Brain and Its Implications for Neurodegenerative Diseases
Saretzki, G. C. (2022) · Stem Cells · doi:10.1093/stmcls/sxac078 · Cited by 13
Kishi, S. (2013) · Translational research · doi:10.1016/j.trsl.2013.10.004 · Cited by 12
Grandjenette, C., Schnekenburger, M., Gaigneaux, A., Gérard, D., Christov, C., Mazumder, A., Dicato, M. A., & Diederich, M. F. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.11.017 · Cited by 12
Advances in Cancer Stem Cell Biology
Scatena, R., Giardina, B., & Mordente, A. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0809-3 · Cited by 13
FOXM1 increases hTERT protein stability and indicates poor prognosis in gastric cancer
Tang, Q., Liu, C., Zhang, S., He, L., Liu, Y., Wang, J., Zhao, X., & Li, X. (2022) · Neoplasia · doi:10.1016/j.neo.2022.100863 · Cited by 11
Cai, Y., Sun, H., Song, X., Zhao, J., Xu, D., & Liu, M. (2023) · Aging · doi:10.18632/aging.205136 · Cited by 11
“It has also been shown that TERT interacts with Brahma-related gene 1 (BRG1) to occupy specific chromatin sites of Wnt/β-catenin target genes, thereby regulating the expression of Wnt pathway target genes [26].”
Noncanonical functions of telomerase and telomeres in viruses‐associated cancer
Rasouli, S., Dakic, A., Wang, Q., Mitchell, D., Blakaj, D. M., Putluri, N., Li, J., & Liu, X. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29665 · Cited by 12
“18 In addition, telomerase's synergistic role with the Wnt/ β ‐ catenin pathway is independent of its catalytic function at telomeres and is essential for maintaining the tumor ‐ initiating cell phenotype in human cancer cells through its interaction with Brg1.”
BackgroundTelomere Reprogramming and Cellular Metabolism: Is There a Link?
Rubtsova, M. P., Никишин, Д. А., Vyssokikh, M. Y., Koriagina, M. S., Vasiliev, A. V., & Dontsova, O. А. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910500 · Cited by 13
Saccharomyces cerevisiae as a model for the study of extranuclear functions of mammalian telomerase
Šimoničová, L., Dudekova, H., Ferenc, J., Procházková, K., Neboháčová, M., Dušinský, R., Nosek, J., & Tomáška, Ľ. (2015) · Current Genetics · doi:10.1007/s00294-014-0472-8 · Cited by 12
“Telomerase was shown to be involved in the control of genes whose products participate in cell cycle, cell signaling, metabolism and apoptosis (Xiang et al. 2002; Smith et al. 2003; Perrault et al. 2005; Rahman et al. 2005; Choi et al. 2008; Yang et al. 2008; Park et al. 2009; Wege et al. 2011; Shkreli et al. 2012; Ia…”
BackgroundChen, W., Wang, G., Guo, J., Sun, L.-A., & Wang, H. (2012) · Stem Cells and Development · doi:10.1089/scd.2012.0121 · Cited by 11
“Wnt and TERT are able to regulate each other [31], and the downregulation of Wnt and TERT may be the result of differentiation of the prostate CSCs in the AIPC cell lines.”
Miller, J., Dakic, A., Spurgeon, M. E., Sáenz, F., Kallakury, B., Zhao, B., Zhang, J., Zhu, J. K., Ma, Q., Xu, Y., et al. (2022) · Journal of Medical Virology · doi:10.1002/jmv.27795 · Cited by 10
“Artandi's laboratory at Stanford has shown that mTERT can not only augment breast cancer development in mice but that it regulates the transcription of genes responsive to the Wnt/beta catenin pathway.(113,114) TERT also exhibits antiapoptotic activity and this activity is independent of telomere‐elongation and telome…”
BackgroundThe Catalytic Subunit of Human Telomerase Is a Unique Caspase-6 and Caspase-7 Substrate
Soares, J., Lowe, M. M., & Jarstfer, M. B. (2011) · Biochemistry · doi:10.1021/bi2010398 · Cited by 11
Zhang, Y., Li, C., Sun, S., Cao, Z., Chen, J., Xiang, H., & Song, L. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/5804710 · Cited by 11
“Increasing evidence has highlighted activities of telomerase that are independent of its conventional function in telomere maintenance which included regulation of cell cycle and gene expression [73–76], inhibition of apoptosis [77], and modulation of cellular signaling such as NF-κB [78].”
BackgroundGiunco, S., Zangrossi, M., Pozzolo, F. D., Celeghin, A., Ballin, G., Petrara, M. R., Amin, A., Argenton, F., Ferreira, M. G., & Rossi, A. D. (2020) · Cancers · doi:10.3390/cancers12082052 · Cited by 11
“While alternative pathways might compensate the non-canonical functions of telomerase in tert−/− embryos, as suggested in the context of Tert−/−mice [29], the acute inhibition of Tert in wt embryos causes the severe effects we observed in our experiments.”
BackgroundKabashima, A., Shimada, S., Shimokawa, M., Akiyama, Y., Tanabe, M., & Tanaka, S. (2020) · Journal of Hepato-Biliary-Pancreatic Sciences · doi:10.1002/jhbp.874 · Cited by 11
Wolf, S. E., Stansberry, K. R., Content, K. R., & Rosvall, K. A. (2021) · Journal of Avian Biology · doi:10.1111/jav.02639 · Cited by 11
Jeensuk, S., Ortega, M. S., Saleem, M. N., Hawryluk, B., Scheffler, T. L., & Hansen, P. J. (2022) · Biology of Reproduction · doi:10.1093/biolre/ioac127 · Cited by 11
“SMARCA4 (also called BRG1) is a chromatin remodeling protein that can be recruited by β-catenin to activate βcatenin target genes including T-cell-specific transcription factor in human cell lines [71] as well as mouse embryonic stem cells [72] and hepatocytes [73].”
BackgroundAn armadillo-domain protein participates in a telomerase interaction network
Dokládal, L., Benková, E., Honys, D., Dupľáková, N., Lee, L., Gelvin, S. B., & Sýkorová, E. (2018) · Plant Molecular Biology · doi:10.1007/s11103-018-0747-4 · Cited by 12
Mišetić, H., Keddar, M. R., Jeannon, J., & Ciccarelli, F. D. (2023) · Genome Medicine · doi:10.1186/s13073-023-01197-0 · Cited by 10
“TERT has been reported to contribute to the WNT-β-catenin pathway through its interaction with the β-catenin transcriptional complex [75], although in a highly context-dependent manner [76].”
BackgroundJayaprasad, A. G., Chandrasekharan, A., Jyothi, S., Sam, S. M. J., Santhoshkumar, T. R., & Pillai, M. R. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130151 · Cited by 10
SIRT1 regulates the localization and stability of telomerase protein by direct interaction
Lee, S. E., Lee, S. B., Roh, J.-I., Kim, K. P., Lee, J. H., & Lee, H. (2024) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2024.150098 · Cited by 10
Genome-wide meta-analysis of heavy menstrual bleeding reveals 36 risk loci
Thibord, F., Cunha, J., Džigurski, J., Tuftin, B., Huffman, J. E., Pujol‐Gualdo, N., Cho, K., Wilson, P. W. F., Johnsen, J. M., Raffield, L. M., et al. (2025) · Blood · doi:10.1182/blood.2024027382 · Cited by 11
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“Puma was under the control of hTERT, a promoter that is active exclusively in the transformed cell lines (22-25).”
BackgroundTelomerase: from Aging to Human Cancers
Parsa, N. (2012) · Springer eBooks · doi:10.1007/978-94-007-4632-9_1 · Cited by 15
TRAPping telomerase within the intestinal stem cell niche
Pech, M. F., & Artandi, S. E. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.51 · Cited by 10
Self-citationCibelli, A., Lopez‐Quintero, S. V., McCutcheon, S., Scemes, E., Spray, D. C., Stout, R. F., Suadicani, S. O., Thi, M. M., & Urban-Maldonado, M. M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.647109 · Cited by 11
Silvestre, D. C., & Londoño‐Vallejo, A. (2012) · Genome dynamics · doi:10.1159/000337128 · Cited by 11
Aono, J., Ruiz‐Rodriguez, E., 青华, Findeisen, H. M., Jones, K. L., Heywood, E. B., & Bruemmer, D. (2016) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2016.01.002 · Cited by 10
“TERT has previously been described to induce gene expression through direct chromatin activation at target gene promoters and interaction with transcription factors (22).”
BackgroundInfluentialNon-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease
Cuevas, R. A., Hortells, L., Chu, C. C., Wong, R., Crane, A., Boufford, C. K., Regan, C., Moorhead, W. J., Bashline, M. J., Parwal, A., et al. (2025) · Circulation Research · doi:10.1161/circresaha.122.321889 · Cited by 11
“18,91,92 We investigated whether SMARCA4 plays a role in the osteogenic reprogramming of hVICs via interacting with TERT.”
Cau, P., Navarro, C. L., Harhouri, K., Roll, P., Sigaudy, S., Kaspi, É., Perrin, S., Sandre‐Giovannoli, A. D., & Lévy, N. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.03.022 · Cited by 10
Telomerase: a good target in hepatocellular carcinoma? An overview of relevant preclinical data
Tornesello, M. L., Tornesello, A. L., Starita, N., Cerasuolo, A., Izzo, F., Buonaguro, L., & Buonaguro, F. M. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2147062 · Cited by 9
“observed between TERT holoenzyme and BRG1-β-catenin complex in the activation of Wnt-driven genes [87].”
BackgroundTelomerase is essential for cardiac differentiation and sustained metabolism of human cardiomyocytes
Chatterjee, S., Leach-Mehrwald, M., Huang, C.-K., Xiao, K., Fuchs, M., Otto, M., Lu, D., Dang, V., Winkler, T., Dunbar, C. E., et al. (2024) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-024-05239-7 · Cited by 9
“TERT is known to bind as a co-factor at the promoter region of several Wnt-dependent targets thereby acting as a transcriptional modulator of the Wnt/β-Catenin signaling cascade [33].”
TERT translocation to mitochondria: Exploring its role in mitochondrial homeostasis
Marinaccio, J., Rossi, E., Micheli, E., Udroiu, I., Baranzini, N., Marcolli, G., & Sgura, A. (2025) · PLoS Genetics · doi:10.1371/journal.pgen.1011923 · Cited by 11
“We included as positive controls proteins known to interact with TERT (pontin/RUVBL1, TPP1/ACD, HSP90, SMARCA4) [18,29–31] and as negative controls, protein almost certainly not interacting with it (hemoglobin alpha/HBA1, meiosis-related MEIOC, histone H2AZ1, desmoplakin/DSP).”
A Comparative Assessment of Replication Stress Markers in the Context of Telomerase
Meessen, S., Najjar, G., Azoitei, A., Iben, S., Bolenz, C., & Güneş, Ç. (2022) · Cancers · doi:10.3390/cancers14092205 · Cited by 9
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Prognostic Parameters for the Primary Care of Melanoma Patients: What Is Really Risky in Melanoma?
Göppner, D., & Leverkus, M. (2011) · Journal of Skin Cancer · doi:10.1155/2011/521947 · Cited by 9
The dual distinct role of telomerase in repression of senescence and myofibroblast differentiation
Harada, M., Hu, B., Lu, J., Wang, J., Rinke, A. E., Wu, Z. B., Liu, T., & Phan, S. H. (2021) · Aging · doi:10.18632/aging.203246 · Cited by 9
Ellis, P. S., Martins, R. R., Thompson, E. J., Farhat, A., Renshaw, S. A., & Henriques, C. M. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00287-8 · Cited by 8
“These so called non-canonical functions of telomerase are important because they are thought to modulate the transcription of genes [22, 23] involved in a wide variety of cellular functions, from DNA repair [24], to enhanced proliferation [25, 26], inhibition of apoptosis [25] enhanced migration [18, 24, 27–31] and in…”
BackgroundInhibition of telomerase activity by NME2: impact on metastasis suppression?
Kar, A., & Chowdhury, S. (2014) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-014-1077-y · Cited by 9
“Authors further demonstrated that resultant activation wnt-beta catenin genes increased the aggressiveness of cells suggesting a non-catalytic function of telomerase that impacts metastasis (Park et al., 2009).”
BackgroundE6 proteins of α and β cutaneous HPV types differ in their ability to potentiate Wnt signaling
Sominsky, S., Shterzer, N., Jackman, A., Shapiro, B., Yaniv, A., & Sherman, L. (2017) · Virology · doi:10.1016/j.virol.2017.05.020 · Cited by 9
Andey, T. A., Attah, M. M., Akwaaba-Reynolds, N. A., Cheema, S., Parvin-Nejad, S., & Acquaah-Mensah, G. K. (2020) · Gene · doi:10.1016/j.gene.2020.100030 · Cited by 9
From infection to immortality: The role of HPV and telomerase in head and neck cancer
Giunco, S., Mistro, A. D., Morello, M., Lidonnici, J., Frayle, H., Gori, S., Rossi, A. D., & Boscolo‐Rizzo, P. (2025) · Oral Oncology · doi:10.1016/j.oraloncology.2024.107169 · Cited by 8
Huo, J., Nie, K., Yang, T., Zhang, S., Zhu, Z., Peng, X., & Zhang, Y. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.119820 · Cited by 9
Wu, L., Wang, S., Tang, B., Tang, L., Lei, Y., Liu, Y., Yang, M., Yang, G., Zhang, D., & Liu, E. (2021) · Journal of Molecular Histology · doi:10.1007/s10735-021-10019-9 · Cited by 8
Protein CD133 as a tumor stem cell marker
Grabovenko, F. I., Валерьевна, К. О., Pavlova, G. V., & Zvereva, M. I. (2022) · Burdenko s Journal of Neurosurgery · doi:10.17116/neiro202286061113 · Cited by 8
Direct cellular targets and anticancer mechanisms of the natural product oridonin
Yao, J., Liu, L., Sun, Q., & Shen, X. (2023) · MedComm – Future Medicine · doi:10.1002/mef2.35 · Cited by 8
Li, S., Qian, X., Fang, G., Deng, Y., Yang, F., Qiu, C., Yang, Y., & Lan, C. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166859 · Cited by 9
Barcenilla, B. B., & Shippen, D. E. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.aw119.008145 · Cited by 8
“Intriguingly, these cells also display altered chromatin structure and fragmented chromosomes, suggesting that TERT plays a role in chromatin reorganization (45).”
BackgroundHelicobacter pylori Induces a Novel NF-kB/LIN28A/let-7a/hTERT Axis to Promote Gastric Carcinogenesis
Li, S., Zeng, J., Ma, L., Li, S., Chen, C., Jia, J., & Liang, X. (2020) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0678 · Cited by 8
“What is more, HCC progenitor cells extracted from premalignant lesions may evolve into CSC and lead to hepatocellular carcinogenesis (50).”
BackgroundCrende, O., García-Gallastegui, P., Luzuriaga, J., Badiola, I., de la Hoz, C., Unda, F., Ibarretxe, G., & Pineda, J. R. (2020) · Biology · doi:10.3390/biology9120426 · Cited by 8
“In turn, telomerase directly modulates Wnt/β-catenin signaling, by activating quiescent stem cells [200].”
BackgroundThe characteristics, tumorigenicities and therapeutics of cancer stem cells based on circRNAs
Zhou, P., Chen, X., Shi, K., Qu, H., & Xia, J. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153822 · Cited by 8
Circulating Virus–Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers
Li, C., Yeh, S., & Chen, P. (2022) · Cancers · doi:10.3390/cancers14102531 · Cited by 9
“TERT can also contribute to carcinogenesis in enzy- matic activity-independent manners, such as promoting β-catenin transcriptional activity through BRG1 [9], amplifying NF-κB-dependent transcription [10], or inhibiting P53 or BCL-2 [11,12].”
BackgroundRamakrishnan, S. K., Varshney, A., Sharma, A., Das, B. C., & Yadava, P. K. (2014) · Tumor Biology · doi:10.1007/s13277-014-1729-z · Cited by 8
“Our results are in line with earlier reports on the role of telomerase in DNA repair [53], senescence-like growth arrest [54], telomere capping [55] resistance to apoptosis [56], regulation of ATR, and its involvement in proliferation signaling [57], Wnt signaling [58], role of hTR in phosphorylation of HnRNP A1 [59],…”
ResultContributions of Telomere Biology to Human Age-Related Disease
Yang, T.-L., Song, S., & Johnson, F. B. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-411596-5.00007-1 · Cited by 9
Transcriptional regulation of the human telomerase reverse transcriptase
Chebel, A., & Ffrench, M. (2010) · Transcription · doi:10.4161/trns.1.1.12062 · Cited by 8
A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules
Thienger, P., Paassen, I., Yao, X., Rubin, P. D., Lehner, M., Lillis, N., Benjak, A., Shah, S. R., Leung, A. K.-Y., de Brot, S., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-2928 · Cited by 8
“Another critical pathway in cancer, especially during developmental processes, is the wingless and int-1 (WNT) pathway, which is partially regulated by the SWI/SNF complex (11).”
Jiang, Y., Chen, C., Chen, S., Wang, Y., Xu, Y. J., Wang, Y., Chen, Z., Xiao, B., & Tao, Z. (2013) · Oncology Letters · doi:10.3892/ol.2013.1344 · Cited by 7
“Park et al (25) reported that TERT interacts with BRG1 to activate transcription of the Wnt/ β -catenin signaling pathway and the downstream target genes.”
Age-related transcriptome changes in melanoma patients with tumor-positive sentinel lymph nodes
Menefee, D. S., McMasters, A., Pan, J., Li, X., Xiao, D., Waigel, S. J., Zacharias, W., Rai, S. N., McMasters, K. M., & Hao, H. (2020) · Aging · doi:10.18632/aging.202435 · Cited by 7
Zhang, G., Zhang, C., Leng, D., Yan, P., Wang, Z., Zhang, M., & Wu, Z. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-021-11564-9 · Cited by 7
The TERT Promoter: A Key Player in the Fight for Cancer Cell Immortality
Hasanau, T. N., Pisarev, E., Валерьевна, К. О., & Zvereva, M. I. (2023) · Biochemistry (Moscow) · doi:10.1134/s000629792314002x · Cited by 9
“On the other hand, telomerase interact with the chromatin-remodeling BRG1 (brahma-related gene 1) protein and promotes its recruitment to the β-catenin-encoding genes followed by the activation of their transcription [97].”
BackgroundPluripotency in the light of the developmental hourglass
Kuijk, E., Geijsen, N., & Cuppen, E. P. J. G. (2014) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/brv.12117 · Cited by 8
“Independent of its catalytic role in adding telomeric repeats, telomerase also induces the expression of WNT pathway components in ES cells (Park et al., 2009).”
BackgroundYamazoe, T., Mori, T., Yoshio, S., & Kanto, T. (2020) · Global Health & Medicine · doi:10.35772/ghm.2020.01089 · Cited by 6
“Thus, mutation in the TERT promoter is one of the important early events of HCC oncogenesis as a tumor initiation, and has close interactions with the MYC, Wnt/β-catenin pathway, and NF-κB pathway (6,34,35).”
BackgroundTERT promoter mutation during development of hepatoblastoma to hepatocellular carcinoma
Dong, R., Zheng, S., & Dong, K. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.045 · Cited by 7
“[3] Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, et al.”
BackgroundSeryl‐ tRNA synthetase inhibits Wnt signaling and breast cancer progression and metastasis
Lei, J., Wang, J., Liu, Z., Zhang, Q., & Yang, X. (2025) · The FASEB Journal · doi:10.1096/fj.202401720r · Cited by 6
“Cancer cell stemness was found enhanced by β - catenin binding to the promoter of the TERT gene 7 and activation of canonical Wnt signaling was found to stabilize SNAI2 and initiate epithelial- to-mesenchymal transition (EMT) transcriptional programs in breast cancer cells.”
Sun, H., Li, X., Long, Q., Wang, X., Zhu, W., Chen, E., Zhou, W., Yang, H., Huang, C., Deng, W., et al. (2024) · iScience · doi:10.1016/j.isci.2024.109869 · Cited by 7
“18 Also, TERT was found to bind at the promoter of the vascular epithelial growth factor (VEGF) gene and promote angiogenesis.”
Akhoundova, D., Fischer, S., Triscott, J., Lehner, M., Thienger, P., Maletti, S., Jacquet, M., Lubis, D. S. H., Bubendorf, L., Jochum, W., et al. (2024) · Diagnostic Pathology · doi:10.1186/s13000-024-01511-3 · Cited by 6
Dahlström, J., Xia, C., Xing, X., Yuan, X., Björkholm, M., & Xu, D. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.04.058 · Cited by 6
Xie, X., Li, M., Zhou, M., Chow, S. F., & Tsang, C. K. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15515 · Cited by 6
“In corroboration with our findings, Artandi's group showed that TERT physically occupies promoters of Wnt- dependent genes in mouse gastrointestinal tract (Park et al., 2009).”
BackgroundDifferential impact of a dyskeratosis congenita mutation in TPP1 on mouse hematopoiesis and germline
Graniel, J. V., Bisht, K. K., Friedman, A. D., White, J. S., Perkey, E., Vanderbeck, A., Moroz, A., Carrington, L. J., Brandstadter, J. D., Allen, F., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202101208 · Cited by 7
“2021), including regulation of wnt signaling (Park et al. 2009), NF-κB-dependent transcription (Ghosh et al.”
BackgroundMajor genomic mutations driving hepatocellular carcinoma
Chen, R., Lin, M., & Gao, D. (2023) · Genome Instability & Disease · doi:10.1007/s42764-023-00103-7 · Cited by 8
“, 2014), which hints at the potential synergistic carcinogenic effect between TERT promoter mutations and WNT/β-catenin pathway mutations (Park et al., 2009).”
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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