Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies
Open accessAbstract
Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized.
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
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?
Neoplastic cells may also achieve genomic instability through short telomeres.
“However, neoplastic cells may also achieve genomic instability through short telomeres.”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [179]
Neoplastic cells can bypass senescence and crisis through oncogenic modifications, eventually upregulating hTERT and increasing telomerase activity, leading to longer telomere length.
“However, oncogenic changes help the cell to bypass senescence and continue divisions until multiple critically shortened telomeres initiate crisis (a period of complete replicative senescence, chromosome end-to-end fusions, and extensive apoptosis). If the neoplastic cell has acquired certain oncogenic modifications, it will overcome the crisis and continue to replicate. Eventually, in many cases,”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [179]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The serial cultivation of human diploid cell strains
Hayflick, L., & Moorhead, P. S. (1961) · Experimental Cell Research · doi:10.1016/0014-4827(61)90192-6 · Cited by 8,508 · see citing works
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091 · cited 1× · see citing works
“telomerase activity in ~90 % of human cancers and cell lines [89], and in 1998 the same team demonstrated that introduction of hTERT”
Self-citationExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975 · see citing works
Self-citationIdentification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400 · see citing works
Olovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847 · see citing works
Highly Recurrent <i>TERT</i> Promoter Mutations in Human Melanoma
Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A. (2013) · Science · doi:10.1126/science.1229259 · Cited by 1,816 · see citing works
<i>TERT</i> Promoter Mutations in Familial and Sporadic Melanoma
Horn, S., Figl, A., Rachakonda, P. S., Fischer, C., Sucker, A., Gast, A., Kadel, S., Moll, I., Nagore, E., Hemminki, K., et al. (2013) · Science · doi:10.1126/science.1230062 · Cited by 1,799 · see citing works
WATSON, J. D. (1972) · Nature New Biology · doi:10.1038/newbio239197a0 · Cited by 1,632 · see citing works
THE STABILITY OF BROKEN ENDS OF CHROMOSOMES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.2.234 · Cited by 1,610 · see citing works
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495 · see citing works
Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H., Gallia, G. L., Giovanella, B. C., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303607110 · Cited by 1,368 · see citing works
Altered Telomeres in Tumors with <i>ATRX</i> and <i>DAXX</i> Mutations
Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., et al. (2011) · Science · doi:10.1126/science.1207313 · Cited by 1,083 · see citing works
Blackburn, E. H., & Gall, J. G. (1978) · Journal of Molecular Biology · doi:10.1016/0022-2836(78)90294-2 · Cited by 1,023 · see citing works
Human Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898 · see citing works
Self-citationFrequency of TERT promoter mutations in human cancers
Vinagre, J., Almeida, A., Pópulo, H., Batista, R., Lyra, J., Pinto, V., Coelho, R., Celestino, R., Prazeres, H., Lima, L., et al. (2013) · Nature Communications · doi:10.1038/ncomms3185 · Cited by 898 · see citing works
Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1
Denchi, E. L., & de Lange, T. (2007) · Nature · doi:10.1038/nature06065 · Cited by 880 · see citing works
Highly prevalent TERT promoter mutations in aggressive thyroid cancers
Liu, X., Bishop, J. A., Shan, Y., Pai, S. I., Liu, D., Murugan, A. K., Sun, H., El‐Naggar, A. K., & Xing, M. (2013) · Endocrine Related Cancer · doi:10.1530/erc-13-0210 · Cited by 614 · see citing works
Vonderheide, R. H., Hahn, W. C., Schultze, J. L., & Nadler, L. M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80066-7 · Cited by 570 · see citing works
The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer
Bell, R. J. A., Rube, H. T., Kreig, A., Mancini, A., Fouse, S. D., Nagarajan, R. P., Choi, S., Hong, C., He, D., Pekmezci, M., et al. (2015) · Science · doi:10.1126/science.aab0015 · Cited by 566 · see citing works
Yan, H., Killela, P. J., Reitman, Z. J., Jiao, Y., Bettegowda, C., Agrawal, N., Diaz, L. A., Friedman, A. H., Friedman, H. S., Gallia, G. L., et al. (2014) · Neuro-Oncology · doi:10.1093/neuonc/nou206.18 · Cited by 530 · see citing works
Role of telomeres and telomerase in cancer
Shay, J. W., & Wright, W. E. (2011) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2011.10.001 · Cited by 523 · see citing works
Self-citationA Human Telomerase Holoenzyme Protein Required for Cajal Body Localization and Telomere Synthesis
Venteicher, A. S., Abreu, E. B., Meng, Z., McCann, K. E., Terns, R. M., Veenstra, T. D., Terns, M. P., & Artandi, S. E. (2009) · Science · doi:10.1126/science.1165357 · Cited by 522 · see citing works
Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors
Flynn, R. L., Cox, K. E., Jeitany, M., Wakimoto, H., Bryll, A. R., Ganem, N. J., Bersani, F., Pineda, J. R., Suvà, M. L., Benes, C. H., et al. (2015) · Science · doi:10.1126/science.1257216 · Cited by 504 · see citing works
Super-Resolution Fluorescence Imaging of Telomeres Reveals TRF2-Dependent T-loop Formation
Doksani, Y., Wu, J. Y., de Lange, T., & Zhuang, X. (2013) · Cell · doi:10.1016/j.cell.2013.09.048 · Cited by 493 · cited 1× · see citing works
“The 3′ G-rich overhang facilitates telomeric DNA in forming a higher-order structure in which the 3′ single-stranded overhang folds back and invades the homologous double-stranded TTAGGG region, forming a telomeric loop (T-loop) that provides 3′-end protection by sequestering it from recognition by the DDR machinery […”
BackgroundWright, W. E., Pereira‐Smith, O. M., & Shay, J. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.3088 · Cited by 478 · see citing works
Self-citationRNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells
Arora, R., Lee, Y., Wischnewski, H., Brun, C. M., Schwarz, T., & Azzalin, C. M. (2014) · Nature Communications · doi:10.1038/ncomms6220 · Cited by 468 · see citing works
Muller, H. J. (1938) · Medical Entomology and Zoology · Cited by 405 · see citing works
Middleton, G., Silcocks, P., Cox, T. F., Valle, J. W., Wadsley, J., PROPPER, D. J., Coxon, F. Y., Ross, P. J., Madhusudan, S., Roques, T. W., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70236-0 · Cited by 380 · see citing works
Telomerase directly regulates NF-κB-dependent transcription
Ghosh, A., Saginc, G., Leow, S. C., Khattar, E., Shin, E. M., Yan, T. D., Wong, M., Zhang, Z., Li, G., Sung, W.-K., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2621 · Cited by 378 · see citing works
Su, Z., Dannull, J., Yang, B. K., Dahm, P., Coleman, D., Yancey, D., Sichi, S., Niedzwiecki, D., Boczkowski, D., Gilboa, E., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.6.3798 · Cited by 359 · see citing works
Rachakonda, P. S., Hosen, M. I., de Verdier, P. J., Fallah, M., Heidenreich, B., Ryk, C., Wiklund, P. N., Steineck, G., Schadendorf, D., Hemminki, K., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310522110 · Cited by 339 · see citing works
Venteicher, A. S., Meng, Z., Mason, P. J., Veenstra, T. D., & Artandi, S. E. (2008) · Cell · doi:10.1016/j.cell.2008.01.019 · Cited by 329 · see citing works
Robin, J. D., Ludlow, A. T., Batten, K. G., Magdinier, F., Stadler, G., Wagner, K. R., Shay, J. W., & Wright, W. E. (2014) · Genes & Development · doi:10.1101/gad.251041.114 · Cited by 327 · see citing works
Self-citationNovel anticancer therapeutics targeting telomerase
Ruden, M., & Puri, N. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.06.007 · Cited by 309 · see citing works
Distribution of TERT promoter mutations in pediatric and adult tumors of the nervous system
Koelsche, C., Sahm, F., Capper, D., Reuß, D., Sturm, D., Jones, D., Kool, M., Northcott, P. A., Wiestler, B., Böhmer, K., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1195-5 · Cited by 302 · see citing works
Human telomerase: biogenesis, trafficking, recruitment, and activationPreprint
Schmidt, J. C., & Cech, T. R. (2015) · Genes & Development · doi:10.1101/gad.263863.115 · Cited by 301 · see citing works
Clynes, D., Jelinska, C., Xella, B., Ayyub, H., Scott, C., Mitson, M., Taylor, S., Higgs, D. R., & Gibbons, R. J. (2015) · Nature Communications · doi:10.1038/ncomms8538 · Cited by 293 · see citing works
<i>TERT</i> promoter mutations and telomerase reactivation in urothelial cancer
Borah, S., Xi, L., Zaug, A. J., Powell, N. M., Dancik, G. M., Cohen, S. B., Costello, J. C., Theodorescu, D., & Cech, T. R. (2015) · Science · doi:10.1126/science.1260200 · Cited by 292 · see citing works
Allory, Y., Beukers, W., Sagrera, A. M. A. D. P., Flández, M., Marqués, M., Márquez, M., van der Keur, K. A., Dyrskjøt, L., Lurkin, I., Vermeij, M., et al. (2013) · European Urology · doi:10.1016/j.eururo.2013.08.052 · Cited by 283 · see citing works
Liu, Z., Li, Q., Li, K., Chen, L., Li, W., Hou, M., Liu, T., Yang, J., Lindvall, C., Björkholm, M., et al. (2013) · Oncogene · doi:10.1038/onc.2012.441 · Cited by 276 · see citing works
<i>In vivo</i> Inhibition of Lung Cancer by GRN163L: A Novel Human Telomerase Inhibitor
Dikmen, Z. G., Gellert, G. C., Jackson, S., Gryaznov, S., Tressler, R., Dogan, P., Wright, W. E., & Shay, J. W. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-1215 · Cited by 271 · see citing works
Self-citationHerbert, B., Gellert, G. C., Hochreiter, A. E., Pongracz, K., Wright, W. E., Zielińska, D., Chin, A. C., Harley, C. B., Shay, J. W., & Gryaznov, S. M. (2005) · Oncogene · doi:10.1038/sj.onc.1208760 · Cited by 269 · see citing works
Self-citationCancer-associated TERT promoter mutations abrogate telomerase silencing
Chiba, K., Johnson, J. Z., Vogan, J. M., Wagner, T., Boyle, J. M., & Hockemeyer, D. F. (2015) · eLife · doi:10.7554/elife.07918 · Cited by 253 · see citing works
Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer
Brunsvig, P. F., Aamdal, S., Klemp, M., Kvalheim, G., Markowski-Grimsrud, C. J., Sve, I., Dyrhaug, M., Trachsel, S., Møller, M., Eriksen, J. A., et al. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0145-7 · Cited by 246 · see citing works
ALTernative Telomere Maintenance and Cancer
Dilley, R. L., & Greenberg, R. A. (2015) · Trends in cancer · doi:10.1016/j.trecan.2015.07.007 · Cited by 241 · see citing works
TERT promoter mutations in cancer development
Heidenreich, B., Rachakonda, P. S., Hemminki, K., & Kumar, R. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.005 · Cited by 238 · see citing works
Reactivation of telomerase in cancer
Akıncılar, S. C., Unal, B., & Tergaonkar, V. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2146-9 · Cited by 223 · see citing works
Marian, C. O., Cho, S. K., Mcellin, B. M., Maher, E. A., Hatanpaa, K. J., Madden, C. J., Mickey, B., Wright, W. E., Shay, J. W., & Bachoo, R. M. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2850 · Cited by 220 · see citing works
Self-citationCusanelli, E., & Chartrand, P. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00143 · Cited by 208 · see citing works
Renaud, S., Loukinov, D. I., Abdullaev, Z., Guilleret, I., Bosman, F. T., Lobanenkov, V. V., & Benhattar, J. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl1125 · Cited by 204 · see citing works
Complex interactions between the DNA-damage response and mammalian telomeres
Arnoult, N., & Karlseder, J. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3092 · Cited by 202 · see citing works
Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation
Li, Y., Zhou, Q.-L., Sun, W., Chandrasekharan, P., Cheng, H. S., Ying, Z., Lakshmanan, M., Raju, A., Tenen, D. G., Cheng, S., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3240 · Cited by 193 · see citing works
Zimmermann, M., Kibe, T., Kabir, S., & de Lange, T. (2014) · Genes & Development · doi:10.1101/gad.251611.114 · Cited by 189 · see citing works
Huang, D.-S., Wang, Z., He, X.-J., Diplas, B., Yang, R., Killela, P. J., Liang, J.-B., Meng, Q., Ye, Z.-Y., Wang, W., et al. (2015) · European Journal of Cancer · doi:10.1016/j.ejca.2015.03.010 · Cited by 184 · see citing works
ATRX represses alternative lengthening of telomeres
Napier, C. E., Huschtscha, L. I., Harvey, A., Bower, K., Noble, J. R., Hendrickson, E. A., & Reddel, R. R. (2015) · Oncotarget · doi:10.18632/oncotarget.3846 · Cited by 182 · see citing works
Noncanonical Functions of Telomerase: Implications in Telomerase-Targeted Cancer Therapies
Li, Y., & Tergaonkar, V. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3568 · Cited by 171 · see citing works
Telomerase regulates MYC-driven oncogenesis independent of its reverse transcriptase activity
Koh, C. M., Khattar, E., Leow, S. C., Liu, C. Y., Müller, J., Ang, W. X., Li, Y., Franzoso, G., Li, S., Guccione, E., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79134 · Cited by 161 · see citing works
Mender, I., Gryaznov, S. M., Dikmen, Z. G., Wright, W. E., & Shay, J. W. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0609 · Cited by 161 · see citing works
Self-citationArchitecture of human telomerase RNA
Zhang, Q., Kim, N.-K., & Feigon, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100279108 · Cited by 157 · see citing works
Telomerase as a universal tumor-associated antigen for cancer immunotherapy
Vonderheide, R. H. (2002) · Oncogene · doi:10.1038/sj.onc.1205074 · Cited by 153 · see citing works
Is telomerase a viable target in cancer?
Buseman, C. M., Wright, W. E., & Shay, J. W. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.07.006 · Cited by 145 · see citing works
Self-citationATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres
Tong, A. S., Stern, J. L., Sfeir, A. J., Kartawinata, M., de Lange, T., Zhu, X., & Bryan, T. M. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.041 · Cited by 136 · see citing works
Reversible Cellular Senescence: Implications for Immortalization of Normal Human Diploid Fibroblasts
Wright, W. E., Pereira‐Smith, O. M., & Shay, J. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.7.3088-3092.1989 · Cited by 136 · see citing works
Self-citationStructural Basis of Telomerase Inhibition by the Highly Specific BIBR1532
Bryan, C., Rice, C., Hoffman, H., Harkisheimer, M. J., Sweeney, M. A., & Skordalakes, E. (2015) · Structure · doi:10.1016/j.str.2015.08.006 · Cited by 131 · see citing works
Telomere Position Effect and Silencing of Transgenes near Telomeres in the Mouse
Pedram, M., Sprung, C. N., Gao, Q., Lo, A. W. I., Reynolds, G. E., & Murnane, J. P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.5.1865-1878.2006 · Cited by 126 · see citing works
Cell death during crisis is mediated by mitotic telomere deprotection
Hayashi, M. T., Cesare, A. J., Rivera, T., & Karlseder, J. (2015) · Nature · doi:10.1038/nature14513 · Cited by 125 · see citing works
Telomerase promoter mutations in cancer: an emerging molecular biomarker?
Vinagre, J., Pinto, V. S., Celestino, R., Reis, M., Pópulo, H., Boaventura, P., Melo, M., Catarino, T. A., Lima, J. P., Lopes, J. M., et al. (2014) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-014-1608-4 · Cited by 120 · see citing works
Control of telomerase action at human telomeres
Hockemeyer, D. F., & Collins, K. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3083 · Cited by 118 · see citing works
TERT promoter mutations contribute to subset prognostication of lower-grade gliomas
Chan, A. K., Yao, Y., Zhang, Z., Chung, N. Y., Liu, J. S.-M., Li, K. K., Shi, Z., Chan, D. T. M., Poon, W. S., Zhou, L., et al. (2014) · Modern Pathology · doi:10.1038/modpathol.2014.94 · Cited by 111 · see citing works
Identification of human TERT elements necessary for telomerase recruitment to telomeres
Schmidt, J. C., Dalby, A. B., & Cech, T. R. (2014) · eLife · doi:10.7554/elife.03563 · Cited by 104 · see citing works
ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells
Lee, S. S., Bohrson, C. L., Pike, A. M., Wheelan, S. J., & Greider, C. W. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.035 · Cited by 102 · see citing works
Lev, A., Denkberg, G., Cohen, C. J., Tzukerman, M., Skorecki, K. L., Chames, P., Hoogenboom, H. R., & Reiter, Y. (2002) · PubMed · Cited by 100 · see citing works
Koelsche, C., Renner, M., Hartmann, W., et al. (2014) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-33-33 · Cited by 98 · see citing works
TERT promoter mutations and monoallelic activation of TERT in cancer
Huang, F. W., Bielski, C. M., Rinne, M. L., Hahn, W. C., Sellers, W. R., Stegmeier, F. P., Garraway, L. A., & Kryukov, G. V. (2015) · Oncogenesis · doi:10.1038/oncsis.2015.39 · Cited by 97 · see citing works
Cancer vaccination with telomerase peptide GV1001
Kyte, J. A. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780902897631 · Cited by 95 · see citing works
Alternative 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 · see citing works
Self-citationMasutomi, K., Kaneko, S., Hayashi, N., Yamashita, T., Shirota, Y., KOBAYASHI, K. P., & Murakami, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000622200 · Cited by 85 · see citing works
Telomerase Inhibitor Imetelstat (GRN163L) Limits the Lifespan of Human Pancreatic Cancer Cells
Burchett, K. M., Yan, Y., & Ouellette, M. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085155 · Cited by 84 · see citing works
Targeting telomerase-expressing cancer cells
Ouellette, M. M., Wright, W. E., & Shay, J. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01279.x · Cited by 82 · see citing works
Self-citationBower, K., Napier, C. E., Cole, S. L., Dagg, R. A., Lau, L. M. S., Duncan, E. L., Moy, E. L., & Reddel, R. R. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050062 · Cited by 81 · see citing works
The effects of telomerase inhibition on prostate tumor‐initiating cells
Marian, C. O., Wright, W. E., & Shay, J. W. (2010) · International Journal of Cancer · doi:10.1002/ijc.25043 · Cited by 78 · see citing works
Self-citationTRF2-Tethered TIN2 Can Mediate Telomere Protection by TPP1/POT1
Frescas, D., & de Lange, T. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.01052-13 · Cited by 78 · see citing works
TERT promoter mutations in renal cell carcinomas and upper tract urothelial carcinomas
Wang, K., Liu, T., Liu, L., Liu, J., Liu, C., Wang, C., Ge, N., Ren, H., Yan, K., Hu, S., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1829 · Cited by 76 · see citing works
Jackson, S. R., Zhu, C.-H., Paulson, V., Watkins, L., Dikmen, Z. G., Gryaznov, S. M., Wright, W. E., & Shay, J. W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2306 · Cited by 72 · see citing works
Self-citationCevik, D. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i1.311 · Cited by 71 · see citing works
Wang, K., Liu, T., Ge, N., Liu, L., Yuan, X., Liu, J., Kong, F., Wang, C., Ren, H., Yan, K., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2660 · Cited by 71 · see citing works
Human Rap1 modulates TRF2 attraction to telomeric DNA
Janoušková, E., Nečasová, I., Pavloušková, J., Zimmermann, M., Hluchý, M., Marini, V., Nováková, M., & Hofr, C. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv097 · Cited by 69 · see citing works
Kotsakis, A. P., Papadimitraki, E., Vetsika, E., Aggouraki, D., Dermitzaki, E. K., Hatzidaki, D., Kentepozidis, N. K., Mavroudis, D., & Georgoulias, V. (2014) · Lung Cancer · doi:10.1016/j.lungcan.2014.07.018 · Cited by 67 · see citing works
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 65 · see citing works
Assembly of telomeric chromatin to create ALTernative endings
O’Sullivan, R. J., & Almouzni, G. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.07.007 · Cited by 64 · see citing works
Inhibition of Telomerase Recruitment and Cancer Cell Death
Nakashima, M., Nandakumar, J., Sullivan, K. D., Espinosa, J. M., & Cech, T. R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.518175 · Cited by 58 · see citing works
Prospects and challenges of building a cancer vaccine targeting telomerase
Vonderheide, R. H. (2007) · Biochimie · doi:10.1016/j.biochi.2007.07.005 · Cited by 55 · see citing works
Beccaria, M. G., Martínez, P., Méndez‐Pertuz, M., Martı́nez, S., Blanco‐Aparicio, C., Cañamero, M., Mulero, F., Ambrogio, C., Flores, J. M., Megı́as, D., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404497 · Cited by 54 · see citing works
Structural basis of template-boundary definition in Tetrahymena telomerase
Jansson, L. I., Akiyama, B. M., Ooms, A. N., Lu, C. C., Rubin, S. M., & Stone, M. D. (2015) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3101 · Cited by 50 · see citing works
Eid, R., Demattei, M.-V., Episkopou, H., Augé‐Gouillou, C., Decottignies, A., Grandin, N., & Charbonneau, M. (2015) · Molecular and Cellular Biology · doi:10.1128/mcb.01317-14 · Cited by 48 · see citing works
Binding of TPP1 Protein to TIN2 Protein Is Required for POT1a,b Protein-mediated Telomere Protection
Frescas, D., & de Lange, T. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.592592 · Cited by 47 · see citing works
Epigenetic control of telomerase and modes of telomere maintenance in aging and abnormal systems
Serene, R. L. (2005) · Frontiers in bioscience · doi:10.2741/1661 · Cited by 46 · see citing works
The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells
Castro‐Vega, L. J., Jouravleva, K., Ortíz-Montero, P., Liu-Bordes, W.-Y., Galeano, J. L., Romero, M. L., Popova, T. G., Bacchetti, S., Vernot, J., & Londoño‐Vallejo, A. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv101 · Cited by 41 · see citing works
Lu, R., Pal, J., Buon, L., Nanjappa, P., Shi, J., Fulciniti, M., Tai, Y.-T., Guo, L., Yu, M., Gryaznov, S. M., et al. (2013) · Oncogene · doi:10.1038/onc.2013.103 · Cited by 40 · see citing works
Frequency of TERT Promoter Mutations in Prostate Cancer
Stoehr, R., Taubert, H. W., Zinnall, U., et al. (2015) · Pathobiology · doi:10.1159/000381903 · Cited by 39 · see citing works
Mender, I., Gryaznov, S. M., & Shay, J. W. (2015) · Oncoscience · doi:10.18632/oncoscience.213 · Cited by 38 · see citing works
Self-citationThe asymmetry of telomere replication contributes to replicative senescence heterogeneity
Bourgeron, T., Xu, Z., Doumic, M., & Teixeira, M. T. (2015) · Scientific Reports · doi:10.1038/srep15326 · Cited by 36 · see citing works
Are Short Telomeres Predictive of Advanced Cancer?
Shay, J. W. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0506 · Cited by 34 · see citing works
Self-citationHu, Y., Bobb, D., He, J., Hill, D. A., & Dome, J. S. (2015) · Cancer Biology & Therapy · doi:10.1080/15384047.2015.1040964 · Cited by 29 · see citing works
Three-dimensional Nuclear Telomere Organization in Multiple Myeloma
Klewes, L., Vallente, R. U., Dupas, E., Brand, C., Grün, D., Guffei, A., Sathitruangsak, C., Awe, J. A., Kuzyk, A. C., Lichtensztejn, D., et al. (2013) · Translational Oncology · doi:10.1593/tlo.13613 · Cited by 24 · see citing works
Lee, J. H., Jeong, S. A., Khadka, P., Hong, J., & Chung, I. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv844 · Cited by 24 · see citing works
Georgoulias, V., Douillard, J., Khayat, D., et al. (2013) · Clinical Lung Cancer · doi:10.1016/j.cllc.2013.02.001 · Cited by 23 · see citing works
Hsu, C., Lee, L., Tang, S., Hsin, I., Lin, Y., & Ko, J. (2015) · Tumor Biology · doi:10.1007/s13277-015-3204-x · Cited by 16 · see citing works
Telomerase activity: An attractive target for cancer therapeutics
Picariello, L. (2014) · World Journal of Pharmacology · doi:10.5497/wjp.v3.i4.86 · Cited by 8 · see citing works
Targeting the Telomere with T-Oligo, G Quadruplex Stabilizers, and Tankyrase Inhibitors
Ivancich, L. W. M. (2014) · Journal of Cancer Science & Therapy · doi:10.4172/1948-5956.1000304 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Telomere-driven diseases and telomere-targeting therapies
Martínez, P., & Blasco, M. A. (2017) · Journal of Cell Biology · doi:10.1083/jcb.201610111 · Cited by 257 · see citing works
“To date, several mechanisms underlying reactivation of telomerase in cancer cells have been described: notably, mutations in TERT promoter, alterations in the alternative splicing of TERT premRNA, gene amplification, epigenetic changes, alterations in regulatory factors, and /or disruption of TPE (Jafri et al., 2016).”
BackgroundInfluentialShort-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80 · see citing works
Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
- Authors
- Jafri, M. A., Ansari, S. A., Alqahtani, M. H., & Shay, J. W.
- Affiliations
- King Abdulaziz University (SA)
- Corresponding author
- Shay, Jerry W.
- Venue
- Genome Medicine
- Published
- 2016-06-20
- Volume
- 8
- Issue
- 1
- Pages
- 69-69
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC4915101
- OpenAlex
- W2465907273
- Cited by
- 716
- References
- 110
- Citations by year
- 2026: 29 · 2025: 66 · 2024: 84 · 2023: 105 · 2022: 96 · 2021: 88 · 2020: 96 · 2019: 67 · 2018: 42 · 2017: 37 · 2016: 4
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P50CA70907)
- National Institute on Aging (AG001228)
- National Center for Research Resources (C06 RR3-414)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- telomeres, telomerase, telomerase reactivation, telomere length control, alternative lengthening of telomeres, ATRX, DAXX, telomerase inhibitors, telomerase assembly, chromosomal instability, carcinogenesis, tumor initiation, anticancer agents
- MeSH terms
- X-linked Nuclear Protein, Antineoplastic Agents, DNA Helicases, Enzyme Inhibitors, Humans, Mutation, Neoplasms, Nuclear Proteins, Promoter Regions, Genetic, Telomere, Molecular Chaperones, Telomerase, Adaptor Proteins, Signal Transducing, Co-Repressor Proteins, Telomere Homeostasis
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
