The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Wnt signalling in stem cells and cancer
Reya, T., & Clevers, H. (2005) · Nature · doi:10.1038/nature03319 · Cited by 3,666
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820
Self-citationDepletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4
Kořínek, V., Barker, N., Moerer, P., van Donselaar, E. V., Huls, G., Peters, P., & Clevers, H. (1998) · Nature Genetics · doi:10.1038/1270 · Cited by 1,704
Essential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270
Lustig, B., Jerchow, B., Sachs, M., Weiler, S., Pietsch, T., Karsten, U., van de Wetering, M., Clevers, H., Schlag, P., Birchmeier, W., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.4.1184-1193.2002 · Cited by 1,198
De Novo Hair Follicle Morphogenesis and Hair Tumors in Mice Expressing a Truncated β-Catenin in Skin
Gat, U., DasGupta, R., Degenstein, L., & Fuchs, E. (1998) · Cell · doi:10.1016/s0092-8674(00)81631-1 · Cited by 1,089
The many ways of Wnt in cancer
Polakis, P. G. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.007 · Cited by 886
Regulation of Telomerase by Telomeric Proteins
Smogorzewska, A., & de Lange, T. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.071403.160049 · Cited by 813
Proteins of the Myc Network: Essential Regulators of Cell Growth and Differentiation
Arsenian‐Henriksson, M., & Lüscher, B. (1996) · Advances in cancer research · doi:10.1016/s0065-230x(08)60353-x · Cited by 781
Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., McCrea, P., Kintner, C., Noro, C., & Wylie, C. (1994) · Cell · doi:10.1016/0092-8674(94)90069-8 · Cited by 693
Self-citation
Cited by
Sorted by citations
Items 101–200 of 710
CHUNG, S. S., Dutta, P., Austin, D., Wang, P., Awad, A., & Vadgama, J. V. (2018) · Oncotarget · doi:10.18632/oncotarget.25993 · Cited by 102
“Telomerase is also known to have a non-canonical function which is driving stemness in the cancer cells, playing a role as a transcription co-factor in transcriptional regulation of Wnt signaling pathway [47].”
BackgroundTelomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria
Chiodi, I., & Mondello, C. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00133 · Cited by 98
Eitan, E., Tichon, A., Gazit, A., Gitler, D., Slavin, S., & Priel, E. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201200212 · Cited by 82
“The active enzyme consists of telomerase reverse transcriptase (TERT), an RNA subunit (TERC) and the dyskerin protein (Cohen et al, 2007; Park et al, 2009).”
Qin, Y., Tang, B., Hu, C.-J., Xiao, Y., Xie, R., Yong, X., Wu, Y.-Y., Dong, H. F., & Yang, S. (2015) · Oncotarget · doi:10.18632/oncotarget.5968 · Cited by 93
Yeh, S., Li, C., Lin, Y.-Y., Ho, M., Wang, Y.-C., Tseng, S.-T., & Chen, P. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.01.001 · Cited by 94
“Telomerase can also promote proliferation through cooperation with bcatenin and promote WNT/b-catenin signaling pathways.(44) The concurrent HBV-TERT/TERT promoter mutation with CTNNB1 mutation in HBV-related HCC and hepatitis C”
BackgroundLudlow, A. T., Ludlow, L. W., & Roth, S. M. (2013) · BioMed Research International · doi:10.1155/2013/601368 · Cited by 93
“have extratelomeric functions, such as acting as a transcription factor or part of a chromatin remodeling complex [118].”
BackgroundTMEM9 promotes intestinal tumorigenesis through vacuolar-ATPase-activated Wnt/β-catenin signalling
Jung, Y., Jun, S., Kim, M. J., Lee, S. H., Suh, H. N., Lien, E. M., Jung, H., Lee, S., Zhang, J., Yang, J., et al. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0219-8 · Cited by 93
Self-citationAlternative splicing regulation of telomerase: a new paradigm?
Wong, M. S., Wright, W. E., & Shay, J. W. (2014) · Trends in Genetics · doi:10.1016/j.tig.2014.07.006 · Cited by 92
“Besides maintaining telomeres, TERT (full-length protein with reverse transcriptase activity) has been shown to have non-telomeric functions [48-50].”
BackgroundPan-cancer analysis identifies telomerase-associated signatures and cancer subtypes
Luo, Z., Wang, W., Li, F., Songyang, Z., Feng, X., Xin, C., Dai, Z., & Xiong, Y. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1035-x · Cited by 92
Telomerase in Cancer: Function, Regulation, and Clinical Translation
Robinson, N. J., & Schiemann, W. P. (2022) · Cancers · doi:10.3390/cancers14030808 · Cited by 105
TERT biology and function in cancer: beyond immortalisation
Pestana, A., Vinagre, J., Sobrinho-Simões, M. A., & Soares, P. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-16-0195 · Cited by 94
Advances and clinical challenges of mesenchymal stem cell therapy
Mei, R., Wan, Z., Yang, C., Shen, X., Wang, R., Zhang, H., Yang, R., Li, J., Song, Y., & Su, H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421854 · Cited by 96
“On one hand, studies have indicated that b -catenin — an essential signaling molecule in the Wnt pathway — enhances telomerase reverse transcriptase (TERT) expression and prevents telomere loss in cancer stem cells (75).”
BackgroundTelomere Maintenance as a Target for Drug Discovery
Sekaran, V. G., Soares, J., & Jarstfer, M. B. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400528t · Cited by 94
Targeting the crosstalks of Wnt pathway with Hedgehog and Notch for cancer therapy
Chatterjee, S., & Sil, P. C. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.02.027 · Cited by 91
Brennan, S. K., Wang, Q., Tressler, R., Harley, C. B., Go, N. F., Bassett, E., Huff, C. A., Jones, R. J., & Matsui, W. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012487 · Cited by 88
“Furthermore, TERT is directly associated with the promoters of Wnt target genes [63].”
BackgroundShort Telomeres in Key Tissues Initiate Local and Systemic Aging in Zebrafish
Carneiro, M. C., Henriques, C. M., Nabais, J., Ferreira, T., Carvalho, T., & Ferreira, M. G. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005798 · Cited by 87
“Emerging evidence implicates a role for telomerase in stimulation of cell proliferation and regeneration, independently of telomere length maintenance, via activation of Wnt signaling [106].”
BackgroundBonifacio, L. N., & Jarstfer, M. B. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012519 · Cited by 87
“In addition, a recent report revealed that hTERT facilitates Wnt signaling by binding BRG1, a histone remodeling protein that signals through the b-catenin pathway, to affect proliferation and cell survival of progenitor cells [28].”
BackgroundInfluentialWnt signaling regulates homeostasis of the periodontal ligament
Lim, W. H., Liu, B., Cheng, D., Williams, B. O., Mah, S., & Helms, J. A. (2014) · Journal of Periodontal Research · doi:10.1111/jre.12158 · Cited by 87
Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review
Dinh, T. N., Parat, M., Ong, Y. S., & Khaw, K. Y. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105666 · Cited by 87
Ip, F. C. F., Ng, Y. P., An, H. J., Ying, D., Pang, H. H., Hu, Y., Chin, A. C., Harley, C. B., Wong, Y. H., & Ip, N. Y. (2014) · Neurosignals · doi:10.1159/000365290 · Cited by 84
Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5
Mora‐Blanco, E. L., Mishina, Y. M., Tillman, E. J., Cho, Y.-J., Thom, C. S., Pomeroy, S. L., Shao, W., & Roberts, C. W. M. (2013) · Oncogene · doi:10.1038/onc.2013.37 · Cited by 83
Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway
Diala, I., Wagner, N., Magdinier, F., Shkreli, M., Sirakov, M., Bauwens, S., Schluth‐Bolard, C., Simonet, T., Renault, V. M., Ye, J., et al. (2013) · EMBO Reports · doi:10.1038/embor.2013.16 · Cited by 81
“Previously, TERT was shown to enhance the transcriptional output of the Wnt pathway [20,21].”
Self-citationSaux, C. J. L., Davy, P. M. C., Brampton, C. N., Ahuja, S. S., Fauce, S. R., Shivshankar, P., Nguyen, H., Ramaseshan, M., Tressler, R., Pirot, Z., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0058423 · Cited by 82
“However we cannot exclude the possibility that up-regulation of TERT and its potential role as a transcriptional modulator of the Wnt/b-catenin signaling pathway is also involved [33].”
BackgroundHrdličková, R., Nehyba, J., Bargmann, W., & Bose, H. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086990 · Cited by 83
“Previously, telomerase function has been linked with the activation of Wnt signaling pathway [25].”
BackgroundEvolutionary mechanism unifies the hallmarks of cancer
Horne, S. D., Pollick, S. A., & Heng, H. H. (2014) · International Journal of Cancer · doi:10.1002/ijc.29031 · Cited by 90
Armstrong, C. A., & Tomita, K. (2017) · Open Biology · doi:10.1098/rsob.160338 · Cited by 83
Quantitative assessment of telomerase components in cancer cell lines
Akıncılar, S. C., Low, K. C., Liu, C. Y., Yan, T. D., Oji, A., Ikawa, M., Li, S., & Tergaonkar, V. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.02.035 · Cited by 80
“…and others have found that besides its canonical role in telomere length extension, hTERT could also regulate transcription, most notably that of the oncogenic Wnt and NF j B signaling pathways [17–19] which are well known to regulate various aspects of cellular physiology and oncogenesis [20,21].”
BackgroundTelomere Maintenance Mechanisms in Cancer: Clinical Implications
Reddel, R. R. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140630101047 · Cited by 82
“Another proposed non-catalytic role of TERT is induction of signaling via the Wnt pathway in mouse and human cells, by interacting with BRG1, a chromatin remodeling protein and by acting as a transcriptional co-factor in a complex with -catenin [70, 71].”
BackgroundhTERT mediates norepinephrine-induced Slug expression and ovarian cancer aggressiveness
Choi, M., Cho, K. H., Lee, S., Bae, Y. J., Jeong, K., Rha, S. Y., Choi, E. J., Park, J. H., Kim, J., Lee, J. S., et al. (2014) · Oncogene · doi:10.1038/onc.2014.270 · Cited by 82
Self-citationReconstructing the molecular life history of gliomas
Barthel, F. P., Wesseling, P., & Verhaak, R. G. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1842-y · Cited by 86
“TERT promoter mutations preferentially occur in tissues with a lower rate of self-renewal and there are numerous reports on the extra-telomeric functions of TERT, including effects on the NF-κB and WNT/β-catenin pathway promoting tumor growth and invasiveness [106, 141, 169].”
BackgroundCau, 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.2014.03.021 · Cited by 80
Telomere-related Markers for Cancer
Yuan, X., Dai, M., & Xu, D. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200106145340 · Cited by 77
Increased telomerase activity and vitamin D supplementation in overweight African Americans
Zhu, H., Guo, D. S., Li, K., Pedersen-White, J., Stallmann-Jorgensen, I. S., Huang, Y., Parikh, S. J., Liu, K., & Dong, Y. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.197 · Cited by 75
Role of the NLRP3 Inflammasome: Insights Into Cancer Hallmarks
Lin, T.-Y., Tsai, M.-C., Tu, W., Yeh, H., Wang, S., Huang, S., & Li, C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.610492 · Cited by 77
“The amplification is achieved by TERT serving as a cofactor of the bcatenin/lymphoid enhancer factor (LEF) transcription factor complex (75).”
BackgroundWnt/β-catenin signaling in colorectal cancer: Is therapeutic targeting even possible?
Disoma, C., Zhou, Y., Li, S., Peng, J., & Xia, Z. (2022) · Biochimie · doi:10.1016/j.biochi.2022.01.009 · Cited by 80
Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics
Yuan, X., & Xu, D. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133338 · Cited by 75
“Moreover, during Xenopus embryo development, TERT is similarly required for proper Wnt/β-catenin signaling and for formation of the anterior–posterior axis [8].”
BackgroundInfluentialShim, H. S., Horner, J. W., Wu, C.-J., Li, J., Lan, Z. D., Jiang, S., Xu, X., Hsu, W.-H., Zal, T., Flores, I. I., et al. (2021) · Nature Aging · doi:10.1038/s43587-021-00146-z · Cited by 73
Dyrk2-associated EDD-DDB1-VprBP E3 Ligase Inhibits Telomerase by TERT Degradation
Jung, H., Wang, X., Jun, S., & Park, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.416792 · Cited by 72
“By gene targeting in mESCs, HA epitope was inserted into start codon of TERT to express HATERT fusion protein (25).”
MethodSelf-citationMACC1—the first decade of a key metastasis molecule from gene discovery to clinical translation
Radhakrishnan, H., Walther, W., Zincke, F., Kobelt, D., Imbastari, F., Erdem, M., Kortüm, B., Dahlmann, M., & Stein, U. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-018-9771-8 · Cited by 76
Stadler, G., Chen, J. C. J., Wagner, K. R., Robin, J. D., Shay, J. W., Emerson, C. P., & Wright, W. E. (2011) · Skeletal Muscle · doi:10.1186/2044-5040-1-12 · Cited by 68
“However, this latter notion has been challenged by the observation of putative non-telomeric activities of hTERT [23-25], with strong evidence for its potential to modulate the Wnt pathway in mice [26].”
BackgroundTelomeres, NAFLD and Chronic Liver Disease
Donati, B., & Valenti, L. V. C. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030383 · Cited by 69
“Consistently, hTERT was found to interact with the same promoter elements recognized by BRG1 and β-catenin [62].”
BackgroundCurrent Insights to Regulation and Role of Telomerase in Human Diseases
Ozturk, M. B., Li, Y., & Tergaonkar, V. (2017) · Antioxidants · doi:10.3390/antiox6010017 · Cited by 68
“Further experiments revealed that TERT and β-Catenin co-associated at the promoters of Wnt/β-Catenin target genes by forming a complex with chromatin remodeler BRG1 (also known as SMARCA4) [86].”
BackgroundNon-canonical Functions of Telomerase Reverse Transcriptase: Emerging Roles and Biological Relevance
Thompson, C. A. H., & Wong, J. M. Y. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200131125110 · Cited by 67
Implications of TERT promoter mutations and telomerase activity in urothelial carcinogenesis
Güneş, Ç., Wezel, F., Southgate, J., & Bolenz, C. (2018) · Nature Reviews Urology · doi:10.1038/s41585-018-0001-5 · Cited by 68
Telomere Lengthening and Other Functions of Telomerase
Rubtsova, M. P., Vasilkova, D. P., Malyavko, A. N., Нарайкина, Ю. В., Zvereva, M. I., & Донцова, О. А. (2012) · Acta Naturae · doi:10.32607/20758251-2012-4-2-44-61 · Cited by 66
Emerging mechanisms progress of colorectal cancer liver metastasis
Zhao, W., Dai, S., Yue, L., Fan, X., Gu, J. H., Dai, X., & Qian, X. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1081585 · Cited by 70
“Studies have shown that b-catenin can bind to the TERT gene promoter in the nucleus and directly increase its expression level, which links the Wnt pathway to telomerase activity (16).”
BackgroundMicroRNA100 Inhibits Self-Renewal of Breast Cancer Stem–like Cells and Breast Tumor Development
Deng, L., Li, S., Bai, S., Chen, J., He, X., Martin-Trevino, R., Chen, S., Li, X., Meng, X., Yu, B., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3710 · Cited by 65
“Previous work indicates that telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] regulates stem cell homeostasis independent of its function at telomeres (42) and that TERT, together with the SWI/SNF complex protein brahma-related gene 1 (BRG1, also called SMARCA4), modulates stem cell homeos…”
BackgroundLaeremans, H., Rensen, S. S., Ottenheijm, H. C. J., Smits, J. F. M., & Blankesteijn, W. M. (2010) · Cardiovascular Research · doi:10.1093/cvr/cvq067 · Cited by 67
hTERT promotes cell adhesion and migration independent of telomerase activity
Liu, H., Liu, Q., Ge, Y., Zhao, Q., Zheng, X., & Zhao, Y. B. (2016) · Scientific Reports · doi:10.1038/srep22886 · Cited by 67
Telomerase as a Therapeutic Target in Cardiovascular Disease
Hoffmann, J., Richardson, G. D., Haendeler, J., Altschmied, J., Andrés, V., & Spyridopoulos, I. (2021) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.120.315695 · Cited by 67
Beck, S. J., Jin, X., Sohn, Y.-W., Kim, J.-K., Kim, S.-H., Yin, J., Pian, X., Kim, S.-C., Nam, D., Choi, Y.-J., et al. (2010) · Molecules and Cells · doi:10.1007/s10059-011-0008-8 · Cited by 65
Wnt Signaling and Aging-Related Heart Disorders
Naito, A. T., Shiojima, I., & Komuro, I. (2010) · Circulation Research · doi:10.1161/circresaha.110.223776 · Cited by 64
In the Wnt-er of life: Wnt signalling in melanoma and ageing
Kaur, A., Webster, M. R., & Weeraratna, A. T. (2016) · British Journal of Cancer · doi:10.1038/bjc.2016.332 · Cited by 64
“In the absence of BRG1, TERT is unable to activate b-catenin and its downstream signalling proteins (Park et al, 2009).”
BackgroundSishc, B. J., Nelson, C. B., McKenna, M. J., Battaglia, C. L. R., Herndon, A. K., Idate, R., Liber, H. L., & Bailey, S. M. (2015) · Frontiers in Oncology · doi:10.3389/fonc.2015.00257 · Cited by 64
“Further investigation is needed to probe underlying mechanisms, but candidate pathways include Wnt/β-catenin signaling, in which hTERT has been shown (albeit controversially) to act as a transcriptional coactivator of β-catenin target genes important for stemness and dedifferentiation (37, 39, 41, 100).”
BackgroundTelomerase reverse transcriptase in the regulation of gene expression
Zhou, J., Ding, D., Wang, M., & Cong, Y. (2014) · BMB Reports · doi:10.5483/bmbrep.2014.47.1.284 · Cited by 63
“teracts with BRG1, a chromatin remodeling factor, to regulate the Wnt/β-catenin signaling pathway (8).”
BackgroundTelomerase: Key regulator of inflammation and cancer
Wu, L., Fidan, K., Um, J., & Ahn, K. S. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104726 · Cited by 62
Yu, J., Yuan, X., Sjöholm, L. K., Liu, T., Kong, F., Ekström, T. J., Björkholm, M., & Xu, D. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.07.013 · Cited by 61
Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC
Longo, M., Paolini, E., Meroni, M., & Dongiovanni, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084173 · Cited by 61
“On the contrary, Pro193Leu substitution did not affect TERT catalytic activity but reduced its chromatin binding capacity [229].”
BackgroundZhou, X. Z., Huang, P., Shi, R., Lee, T. H., Lu, G. H., Zhang, Z., Bronson, R. T., & Lu, K. P. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43452 · Cited by 62
Telomeres and Telomerase in the Control of Stem Cells
Lupatov, A. Y., & Yarygin, K. N. (2022) · Biomedicines · doi:10.3390/biomedicines10102335 · Cited by 64
Sun, L., Zhang, X., Wu, S., Liu, Y., Guerrero‐Juarez, C. F., Liu, W., Huang, J., Yao, Q., Yin, M., Li, J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112647 · Cited by 61
Liu, C., Liu, Z., Chen, T., Zeng, W., Guo, Y., & Huang, T. (2016) · Scientific Reports · doi:10.1038/srep36990 · Cited by 62
Ko, E., Seo, H., & Jung, G. (2017) · Hepatology · doi:10.1002/hep.29604 · Cited by 60
“For example, telomerase has been reported to regulate nuclear factor kappa B pathway-dependent expression((32,33)) and Wnt/b-catenin pathway targeting gene expression.((34)) In this study, we emphasize the importance of the telomere-lengthening function of telomerase in human HCC progression, where most of the maligna…”
BackgroundThe non-canonical functions of telomerase: to turn off or not to turn off
Romaniuk-Drapała, A., Paszel-Jaworska, A., Totoń, E., Lisiak, N., Hołysz, H., Królak, A., Grodecka-Gazdecka, S., & Rubiś, B. (2018) · Molecular Biology Reports · doi:10.1007/s11033-018-4496-x · Cited by 66
TERT promoter mutations and GABP transcription factors in carcinogenesis: More foes than friends
Yuan, X., Dai, M., & Xu, D. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.07.003 · Cited by 59
Implications of telomere‐independent activities of telomerase reverse transcriptase in human cancer
Ding, D., Zhou, J., Wang, M., & Cong, Y. (2013) · FEBS Journal · doi:10.1111/febs.12258 · Cited by 61
PITX2 deficiency and associated human disease: insights from the zebrafish model
Hendee, K., Sorokina, E. A., Muheisen, S., Reis, L. M., Tyler, R. C., Marković, V., Čuturilo, G., Link, B. A., & Semina, E. V. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy074 · Cited by 58
“Analysis of the entire list of significantly (x2 or more) downregulated targets identified six WNT transcripts— wnt3, wnt4a, wnt6b, wnt7aa, wnt9b and wnt10a, as well as multiple transcripts of tert encoding a transcriptional modulator of WNT/beta-catenin signaling (45), and seven collagen transcripts, col1a1a, col1a2,…”
BackgroundTelomeres in Plants and Humans: Not So Different, Not So Similar
Schrumpfová, P. P., Fojtová, M., & Fajkus, J. (2019) · Cells · doi:10.3390/cells8010058 · Cited by 61
“Human telomerase and human ARM proteins play a role in the Wnt/APC/β-catenin signaling pathway [168].”
BackgroundBerrino, E., Angeli, A., Zhdanov, D. D., Kiryukhina, A. P., Milaneschi, A., Luca, A. D., Bozdağ, M., Carradori, S., Selleri, S., Bartolucci, G., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00636 · Cited by 58
Kannan, N., Huda, N., Tu, L., Droumeva, R., Aubert, G., Chavez, E. A., Brinkman, R. R., Lansdorp, P. M., Emerman, J. T., Abe, S., et al. (2013) · Stem Cell Reports · doi:10.1016/j.stemcr.2013.04.003 · Cited by 57
“On the other hand, the relatively high levels of telomerase activity found in LPs may have novel, telomere-length-independent roles, as suggested by others (Elenbaas et al., 2001; Hemann et al., 2001; Kiyono et al., 1998; Park et al., 2009; Sharma et al., 2003; Smith et al., 2003).”
BackgroundTelomerase reverse transcriptase moonlights: Therapeutic targets beyond telomerase
Maida, Y., & Masutomi, K. (2015) · Cancer Science · doi:10.1111/cas.12806 · Cited by 58
Tang, B., Xie, R., Qin, Y., Xiao, Y., Yong, X., Zheng, L., Dong, H. F., & Yang, S. (2015) · Oncotarget · doi:10.18632/oncotarget.6575 · Cited by 57
“Previous studies demonstrated that hTERT was able to interact with BRG1 to activate Wnt-dependent target genes [25], bind to the NF-κB p65 subunit [26], and interact with β-catenin to enhance its nuclear localization and transcriptional activity [13].”
BackgroundAhearn, T. U., Shaukat, A., Flanders, W. D., Rutherford, R. E., & Bostick, R. M. (2012) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-12-0292 · Cited by 56
“These results are in line with our reports that suggested that calcium and/or vitamin D3 treatment reduced hTERT expression (a potential cofactor in the β-catenin transcriptional complex (34)) and increased p21 expression (which is negatively regulated by β-catenin/TCF signaling (35)) (36).”
ResultMahfouz, N., Tahtouh, R., Alaaeddine, N., Hajj, J. E., Sarkis, R., Hachem, R. Y., RAAD, I. I., & Hilal, G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179202 · Cited by 56
The dyskerin ribonucleoprotein complex as an OCT4/SOX2 coactivator in embryonic stem cells
Fong, Y. W., Ho, J. J., Inouye, C. J., & Tjian, R. (2014) · eLife · doi:10.7554/elife.03573 · Cited by 54
“…genes, TERT may function to tether the DKC1 complex (as part of the telomerase RNP) to gene promoters and activate transcription by binding to a β-catenin-TCF3 activating complex (Park et al., 2009), an integral component of the core stem cell-specific regulatory circuitry (Cole et al., 2008).”
BackgroundTelomere homeostasis in mammalian germ cells: a review
Reig‐Viader, R., Garcia-Caldés, M., & Ruiz‐Herrera, A. (2015) · Chromosoma · doi:10.1007/s00412-015-0555-4 · Cited by 59
CHUNG, S. S., Oliva, B., Dwabe, S., & Vadgama, J. V. (2016) · International Journal of Oncology · doi:10.3892/ijo.2016.3546 · Cited by 57
“This is in agreement with the recent finding that telomerase acts as a transcriptional modulator of the Wnt-β-catenin signaling pathway in stem cells and cancer cells (20,21).”
BackgroundTümpel, S., & Rudolph, K. L. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06547.x · Cited by 59
Listerman, I., Gazzaniga, F. S., & Blackburn, E. H. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00844-13 · Cited by 56
“previously suggested that TERT expression promotes Wnt signaling (13).”
BackgroundMethodResultInfluentialAssociation between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis
Mosrati, M. A., Willander, K., Falk, I. J., Hermanson, M., Höglund, M., Stockelberg, D., Wei, Y., Lotfi, K., & Söderkvist, P. (2015) · Oncotarget · doi:10.18632/oncotarget.4668 · Cited by 54
“TERT also possess telomere independent functions in tumor formation and other human diseases, regulating Wnt-dependent transcription [12], mitochondrial function and apoptosis [13] and DNA damage response [14].”
BackgroundBennaceur, K., Atwill, M., Al Zhrany, N., Hoffmann, J., Keavney, B., Breault, D., Richardson, G., von Zglinicki, T., Saretzki, G., & Spyridopoulos, I. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.07.020 · Cited by 51
The Solo Play of TERT Promoter Mutations
Hafezi, F., & Perez-Bercoff, D. (2020) · Cells · doi:10.3390/cells9030749 · Cited by 54
“Indeed, TERT also contributes to cell survival and proliferation through telomere-independent mechanisms; it facilitates Wnt/β-catenin-dependent [136,137], c-myc-dependent [138,139], and NF-κB-dependent gene transcription [140,141], thereby sustaining both oncogenic signaling pathways and its own transcription in a fe…”
BackgroundRafat, A., Asl, K. D., Mazloumi, Z., Movassaghpour, A. A., Talebi, M., Shanehbandi, D., Farahzadi, R., Nejati, B., & Charoudeh, H. N. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120402 · Cited by 53
Liang Cheng, C., Zhang, S., Wang, M., & Antonio Lopez-beltran, B. (2022) · Human Pathology · doi:10.1016/j.humpath.2022.06.005 · Cited by 57
Buch, S., Innes, H. A., Lutz, P. L., Nischalke, H. D., Marquardt, J. U., Fischer, J., Weiss, K. H., Rosendahl, J., Marot, A., Krawczyk, M. J., et al. (2022) · Gut · doi:10.1136/gutjnl-2022-327196 · Cited by 53
Molecular regulation of telomerase activity in aging
Nicholls, C., Li, H., Wang, J.-Q., & Liu, J. (2011) · Protein & Cell · doi:10.1007/s13238-011-1093-3 · Cited by 57
“…TERTas a component of a transcription regulation complex that binds chromatin and activates Wnt/β-catenin target genes offers a mechanism that potentially explains these effects, and gives further support to the hypothesis that suggests extratelomeric roles for TERT/telomerase (Park et al., 2009).”
PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis
Jun, S., Lee, S., Kim, H.-C., Ng, C., Schneider, A. M., Ji, H. L., Ying, H., Wang, H., DePinho, R. A., & Park, J. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.09.026 · Cited by 76
“Gene expression analysis was performed, as previously performed (Park et al., 2009).”
MethodSelf-citationSekiguchi, M., Seki, M., Kawai, T., Yoshida, K., Yoshida, M., Isobe, T., Hoshino, N., Shirai, R., Tanaka, M., Souzaki, R., et al. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0125-y · Cited by 48
Ghareghomi, S., Ahmadian, S., Zarghami, N., & Kahroba, H. (2020) · Biochimie · doi:10.1016/j.biochi.2020.11.015 · Cited by 53
Chen, C., Akiyama, K., Yamaza, T., You, Y., Xu, X., Li, B., Zhao, Y., & Shi, S. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303000 · Cited by 53
“Moreover, it is well known that TERT can regulate the Wnt/ b -catenin pathway (Choi et al , 2008; Park et al , 2009).”
InfluentialDonati, B., Pietrelli, A., Pingitore, P., Dongiovanni, P., Caddeo, A. M., Walker, L., Baselli, G., Pelusi, S., Rosso, C., Vanni, E., et al. (2017) · Cancer Medicine · doi:10.1002/cam4.1078 · Cited by 55
“For example, hTERT can act as a transcription factor in the Wntβcatenin signaling pathway, regulating the expression of procarcinogenic Wnt target genes [44].”
BackgroundLiu, Y., Shi, Y., Liu, Y., Pan, X., & Zhang, K. (2018) · Acta Pharmacologica Sinica · doi:10.1038/s41401-018-0007-9 · Cited by 53
TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment
Mao, J., Zhang, Q., Wang, Y., Yang, Z., Xu, L., Ma, X., Guan, D., Zhou, J., Liu, J., Wu, X., et al. (2022) · EMBO Reports · doi:10.15252/embr.202152984 · Cited by 51
“Recent progress from our and other groups suggests a critical role for TERT in tumorigenesis, apart from its function in telomere maintenance (Park et al , 2009; Ghosh et al , 2012; Ding et al , 2013; Liu et al , 2013, 2016).”
Ale‐Agha, N., Dyballa‐Rukes, N., Jakob, S., Altschmied, J., & Haendeler, J. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.02.011 · Cited by 49
“Amongst other things, TERTwas shown to be involved in the regulation of gene expression (Geserick et al., 2006; Park et al., 2009; Smith et al., 2003).”
Senescence: an antiviral defense that is tumor suppressive?
Reddel, R. R. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp274 · Cited by 52
Wang, N., Kjellin, H., Sofiadis, A., Fotouhi, O., Juhlin, C. C., Bäckdahl, M., Zedenius, J., Xu, D., Lehtiö, J., & Larsson, C. (2016) · Oncotarget · doi:10.18632/oncotarget.7237 · Cited by 50
“One of such TERT functions is to serve as a co-factor, promoting beta-catenin target gene transcription [25, 27].”
BackgroundThe Importance of Constraints and Control in Biological Mechanisms: Insights from Cancer Research
Bechtel, W. (2018) · Philosophy of Science · doi:10.1086/699192 · Cited by 49
“The Wnt pathway is important in regulating the cell cycle as it activates replication in stem cells (Park et al. 2009; Bryja, Červenka, and Čajánek 2017).”
BackgroundIntratumoral diversity of telomere length in individual neuroblastoma tumors
Pezzolo, A., Pistorio, A., Gambini, C., Haupt, R., Ferraro, M., Erminio, G., Bernardi, B. D., Garaventa, A., & Pistoia, V. (2014) · Oncotarget · doi:10.18632/oncotarget.2115 · Cited by 54
“48), suggesting that the unfavorable prognosis of NB patients with high hTERT expression may be related to telomerase functions other than telomere elongation [6], such as i) transcriptional modulation of Wnt/ β-catenin signaling pathway [45]; ii) enhancement of cell proliferation and/or resistance to apoptosis [45];…”
Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer
Yang, R., Han, Y., Guan, X., Hong, Y., Meng, J., Ding, S., Qian, L., & Yi, W. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01244-8 · Cited by 50
“Additionally, hTERT can influence Wnt/β-catenin signaling through its interaction with BRG1 [143], although research focusing on this aspect in breast cancer cells is limited.”
BackgroundWu, X., Huang, C., He, X., Tian, Y., Zhou, D., He, Y., Liu, X., & Li, J. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.08.009 · Cited by 49
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
