doi:10.1080/21645515.2015.1012032. J Chem Inf Model (2016) 56:2093102. 
lipoprotein (LDL) cholesterol (. It is essential for embryonic development and it is expressed in normal somatic cells. Genetic pathway of major depressive disorder in shortening telomeric length. Parkinson EK, Fitchett C, Cereser B. Dissecting the non-canonical functions of telomerase. Signal Transducer and Activator of Transcription 3 (STAT3) Regulates Human Telomerase Reverse Transcriptase (hTERT) Expression in Human Cancer and Primary Cells. Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, et al. Moro L. Mitochondrial Dysfunction in Aging and Cancer. (2020). Stoehr R, Taubert H, Zinnall U, Giedl J, Gaisa NT, Burger M, et al. In humans, it is found in some tissues, such as male germ cells, activated lymphocytes, and certain types of stem cell populations. Same word also means what is being talking or written about for example vary in presentation, severity, number! Thus, telomerase represents an attractive target for highly selective cancer therapeutics. Mad1 destabilizes p53 by preventing PML from sequestering MDM2. Definition. Tumour Biol J (2016) 37:49017. Carcano FM, Vidal DO, van Helvoort Lengert A, Neto CS, Queiroz L, Marques H, et al. Falcon Aviation Rc, Am J Lifestyle Med. Co-occurrence of these mutations may support creation of tumors with poor prognosis (10). GSC is a TERT activator and was variously expressed in both thyroid cancer and normal thyroid cells. Chromosome translocations, gene amplification, retroviral insertion or mutations of MYC gene are tumorigenic in mice and correlate with development of most human cancers (93, 94). They are associated with gene expression and phenotype by affecting gene copy number (17). Immunity. Taking in to account its major importance in cancer, TERT has become a target of various therapeutic strategies in cancer treatment and continues to be an interesting object of research. Identification of seven loci affecting mean telomere length and their asso-ciation with disease. doi:10.1038/sj.onc.1203476, 108. de Haas N, de Koning C, di Blasio S, Flrez-Grau G, de Vries IJM, Hato SV. J Clin Endocrinol Metab (2014) 99(8):E15719. Rowland TJ, Dumbovi G, Hass EP, Rinn JL, Cech TR. Clin Cancer Res (2005) 11:43317. Copyright 2022 by the American Association for Cancer Research. These roles can be grouped into two broad categories: a) involving telomerase activity but not telomere elongation and b) involving neither telomere elongation nor telomerase activity (177). George SL, Parmar V, Lorenzi F, Marshall LV, Jamin Y, Poon E, et al. Therapeutic strategies for targeting telomerase Approaches to targeting telomerase include: 1. Additional studies using methods that permit histological localization will help determine whether a specific neoplastic transition correlates with telomerase expression or whether telomerase activation occurs at distinct times in different types of cancers. doi:10.1002/jmri.26964, 56. Aside from the better-known telomere lengthening function, TERT also has many secondary, telomere-independent roles (non-canonical functions of TERT). Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. However, BIBR1532 has not yet progressed to clinical tests (201). Koziel JE, Fox MJ, Steding CE, Sprouse AA, Herbert BS. Overexpression of goosecoid homeobox is associated with chemoresistance and poor prognosis in ovarian carcinoma. Nassir N. A telomerase with novel non-canonical roles: TERT controls cellular aggregation and tissue size in Dictyostelium. Variability within the human TERT gene, telomere length and predisposition to chronic lymphocytic leukemia. Comput Struct Biotechnol J (2020) 18:193946. Rise in insulin resistance is associated with escalated telomere attrition. Alternatively, others have argued that because hTERT expression can be observed at relatively early stages of dysplasia, telomere shortening and selection for telomerase activation may occur before the selection of the complete set of critical mutations that are needed to program malignant growth (14). Hahn W. C., Counter C. M., Lundberg A. S., Beijersbergen R. L., Brooks M. W., Weinberg R. A. Epigenetics describes stable, and possibly heritable changes in activity and expression, which are not associated with any underlying changes in DNA sequence (58). Furthermore, WT1 binding to TERTp suppresses c-MYC level at both protein, and mRNA level (1, 2). A relationship was shown between the level of telomerase activity and increased resistance to therapeutic treatment along with a subsequent poor prognosis for cancer patients [6,7,8], partly because telomerase supports cell survival by suppressing apoptotic signaling . Epub 2005 Nov 17. In 2018, there were 18.1 million cancer cases worldwide and 9.6 million deaths. Ameri Z, Ghiasi S, Farsinejad A, Hassanshahi G, Ehsan M, Fatemi A. Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes. Therefore, in this study, the distribution of dyskerin in a large series of human tumours from the lung, breast, and colon, as well as from B-cell lymphomas, was Raising the bar in anticancer therapy: recent advances in, and perspectives on, telomerase inhibitors. They hypothesized that presence of this mutation coupled with low TERTp methylation discourages H3K27me3 histone methylation in transcriptionally active TERT (70). Liu L, Lai S, Andrews LG, Tollefsbol TO. Aramburu T, Plucinsky S, Skordalakes E. POT1-TPP1 telomere length regulation and disease. Oncol Rep (2014) 32:127380. Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer. Listerman I, Sun J, Gazzaniga FS, Lukas JL, Blackburn EH. Association between previously identified loci affecting telomere length and coronary heart disease (CHD) in Han Chinese population. Increased telomerase activity and comprehensive lifestyle Wang N, Xu D, Sofiadis A, Hoog A, Vukojevic V, Backdahl M, et al. These two expression patterns appeared to be specific for many cancers, although some cancers exhibited variation between MAE and BAE in differed cell lines (34). 1994;266:20115. 
Vaccine (2017) 35:576875. Disclaimer. Baird DM. The two most common TERTp mutations are C>T transitions, located at -124 bp, and -146 bp from the transcription start site (TSS). 7. Recent studies increasingly suggest that epigenetic mechanisms may be targeted in new therapeutic strategies. Cancer 1997, 33, 787791. Wu L, Fidan K, Um JY, Ahn KS. Nat Rev Mol Cell Biol (2011) 12:25965. Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, et al. WebTelomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. Of the seven human STAT encoding genes, STAT3 has drawn the most interest for its association with a wide variety of human cancers (104, 108). demonstrated that the endoplasmic reticulum transiently activates the expression of TERT in cancer cell lines (185). Phytomedicine (2019) 56:94102. Genet Test Mol Biomarkers (2020) 24:1817. STRATEGMED3/306853 from the National Centre for Research and Development, Warsaw, Poland. Leo R, Apolnio JD, Lee D, Figueiredo A, Tabori U, Castelo-Branco P. Mechanisms of human telomerase reverse transcriptase (hTERT) regulation: clinical impacts in cancer. WebTelomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. Telomeres are important cellular structures whose integrity is essential for maintaining cell viability. Curr Opin Hematol. J Mol Endocrinol (2017) 58:R12946. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. doi:10.1038/nrc3025, 4. Department of Adult Oncology, Dana-Farber Cancer Institute and Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115. (grant number K01AT004199; Bethesda, MD, USA); Bahna Foundation (Stamford, CT, USA); doi:10.1111/iji.12182, 160. In contrast, telomerase activity is silenced in most adult somatic cells. Trifa AP, Bnescu C, Tevet M, Bojan A, Dima D, Urian L, et al. This study is registered on the ClinicalTrials.gov website, number NCT00739791. Expert Opin Ther Pat (2016) 26:67988. doi:10.1002/cbin.10826, 86. 2007 Apr-May;25(3):197-208. doi: 10.1080/07357900701208683. Cancer Prev Res (Phila) (2011) 4:124354. Schrank Z, Khan N, Osude C, Singh S, Miller RJ, Merrick C, et al. Zhang F, Cheng D, Wang S, Zhu J. If too much replication stress occurs in ALT cells, as in the case of FANCM depletion, for example [141,142], ALT activity is increased to the point of toxicity and cells cannot survive. Section 1734 solely to indicate this fact. An increase in telomerase activity in one context could be viewed as beneficial because it might lead to an increase in relative telomere length, although Increased telomerase activity and elevated hTERT mRNA expression during multistage carcinogenesis of squamous cell carcinoma of the lung - Shibuya - 2001 - Cancer - doi:10.1089/thy.2020.0055, 30. Allele A was also found to be significantly associated with risk of bladder cancer in the North Indian population (156). The unique feature of telomerase is its low or nonexistent expression in somatic cells, but overexpression in most cancer cells (191). Common germline variation at the TERT locus contributes to familial clustering of myeloproliferative neoplasms. Fujii T, Khawaja MR, DiNardo CD, Atkins JT, Janku F. Targeting isocitrate dehydrogenase (IDH) in cancer. Gay-Bellile M, Vronse L, Combes P, Eymard-Pierre E, Kwiatkowski F, Dauplat MM, et al. Oncol Rep (2014) 32:18998. WebIn one experiment, researchers blocked telomerase activity in human breast and prostate cancer cells growing in the laboratory, prompting the tumor cells to die. Serrano D, Bleau AM, Fernandez-Garcia I, Fernandez-Marcelo T, Iniesta P, Ortiz-de-Solorzano C, et al. Int J Cancer (2002) 101:33541. Oncotarget (2016) 7:2133246. Gaspar TB, S A, Lopes JM, Sobrinho-Simes M, Soares P, Vinagre J. Telomere Maintenance Mechanisms in Cancer. 4. The Shelterin complex plays a fundamental role in protecting chromosome ends and in telomere length regulation (3, 4). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 5. Sci Rep (2015) 5:8201. doi:10.1038/srep08201, 81. Interestingly, one study showed that TERTp hypermethylation was present in both melanoma and normal skin cells. miRNA recognition sites are typically located in 3 untranslated regions (3UTRs) of mRNA (Figures 1 and 2). Jie MM, Chang X, Zeng S, Liu C, Liao GB, Wu YR, et al. TERT import depends on membrane potential and it is located close to the inner membrane (181). 
Sp1 belongs to the family of nuclear proteins called Sp/KLF (specificity protein/Krppel-like factor) that binds GC-(GGGGCGGGG) and GT-(GGTGTGGGG) rich elements (98, 99). During mitosis, MAD1 localizes to unattached kinetochores, where it serves as a docking site for MAD2. a word used to describe someone who is really fake looking or acting. Cancer Treat Rev (2013) 39:44456. The TERT rs2736100 Polymorphism and Susceptibility to Myeloproliferative Neoplasms: A Systematic Review and Meta-Analysis. In this model, telomerase activation occurs after the selection of mutations that stimulate abnormal cell proliferation, and, thus, telomerase activation may be a relatively late event in tumor initiation that allows for genome stability after the acquisition of cancer-associated mutations. Huang G, Geng J, Wang R, Chen L. Identification of a new cytotoxic T-cell epitope p675 of human telomerase reverse transcriptase. While the C allele is primarily associated with cancers, the A allele, which is linked to shorter telomeres, is generally associated with predisposition to degenerative diseases (144). eCollection 2016 Jul-Aug. Franzke B, Neubauer O, Cameron-Smith D, Wagner KH. The commonly utilized method for its detection is polymerase chain re These somatic mutations occur at arginine residues of the IDH active site (namely, IDH1R132H, IDH2R140Q, and IDH2R172K) (53). TERTp lacks a TATA box but it contains binding sites for many different transcription factors (7). 201. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. doi:10.1016/j.phymed.2018.09.218, 214. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Stern JL, Paucek RD, Huang FW, Ghandi M, Nwumeh R, Costello JC, et al. Of arthrogryposis that vary in presentation, severity, and a number involved! In cancer cells, TERTp mutations are generally associated with higher TERT expression level. 200. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. 2010 Jun 13;151(24):965-70. doi: 10.1556/OH.2010.28899. Found on the hands, fingers, feet, or arthrogryposis multiplex congenital, is syndrome. Drug Discovery Today (2020) 25:121322. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, P50 CA174523/CA/NCI NIH HHS/United States, P50CA174523/U.S. doi:10.1073/pnas.1310522110, 153. doi:10.1016/j.vaccine.2017.09.011, 202. When they analyzed tissue sections using in situ RT-PCR, they found that sections derived from tissues with normal or mild dysplasia lacked hTERT transcripts, whereas sections taken from tissues with moderate or severe dysplasia or SCC expressed hTERT. They are encoded by the FABP4 gene. Furthermore, a major study specifically focusing on TERT gene amplification found it to occur in many cancers, such as esophageal, ovarian cancer, and squamous cell carcinoma (12). 
Life Sci (2020) 250:117550. doi:10.1016/j.lfs.2020.117550, 213. doi:10.1016/j.gene.2004.06.011, 130. Exp Rev Mol Med (2010) 12:e16. A significant feature of dyskeratosis congenita is an increased susceptibility to cancer; so far, however, no data have been reported on dyskerin changes in human tumours. and transmitted securely. 8600 Rockville Pike Front Genet (2016) 7:83. doi:10.3389/fgene.2016.00083, 60. *Correspondence: Marta Dratwa, marta.dratwa@hirszfeld.pl; Katarzyna Bogunia-Kubik, katarzyna.bogunia-kubik@hirszfeld.pl, Genetic and Epigenetic Control on Immune Responses Regulating Molecules in Cancer Development, Progression, and Treatment, View all
Singh V, Jaiswal PK, Mittal RD. Depending on the number tandem repeats, promoter activity is affected differently. Nutrients. 2012 Feb 1;730(1-2):90-7. doi: 10.1016/j.mrfmmm.2011.07.006. AK, USA); Jeff Walker Family Foundation (Wilton, CT, USA); Safeway Foundation (Pleasanton, Oncotarget (2016) 7:5772636. Exp Cell Res (2020) 396:112298. doi:10.1016/j.yexcr.2020.112298, 42. eCollection 2022. DeJoria Foundation (Los Angeles, CA, USA); Kerzner Foundation (New York, NY, USA); Methods: Our previous work showed that the S variant was more frequent in non-Hodgkins B-cell lymphoma patients how did not respond to treatment, as well as those with intermediate/high International Prognostic Index (159). Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas. The increases Although almost certainly correct in its broad outlines, several disparate observations require further investigation. Hypermethylation in this exonic region is common in most cancers, and CTCF is considered a major TERT repressor in normal cells. Despite the above considerations, the observation that hTERT was expressed in squamous epithelial cells at a specific histological transition (from mild to moderate dysplasia) begins to address the biological question of when during the stepwise progression of normal cells into cancer cells does hTERT become activated. Both of these splice sites result in TERT proteins that are incapable of telomere elongation (169172). A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction. Gurung RL, Lim HK, Venkatesan S, Lee PSW, Hande MP. TERT can also interact with mitochondrial RNA processing endoribonuclease (RMRP) and use the RNA-dependent RNA polymerase to synthesize dsRNA. Accessibility Romaniuk A, Paszel Jaworska A, Toto E, Lisiak N, Hoysz H, Krlak A, et al. Characterization of Allele-Specific Regulation of Telomerase Reverse Transcriptase in Promoter Mutant Thyroid Cancer Cell Lines. BMC Cancer (2010) 10:571. doi:10.1186/1471-2407-10-571, 169. They mean here about the different types of poop, which has a of! Yamada O, Kawauchi K. The role of the JAK-STAT pathway and related signal cascades in telomerase activation during the development of hematologic malignancies. Other major TERT regulation mechanisms (also known as telomere maintenance mechanisms) are: chromosome rearrangements, methylation, miRNA interference, binding of transcription factors, genetic polymorphism, and alternative splicing. Of non-persimmon species of the genus are grown for ebony timber and.! Int J Mol Sci (2015) 16:1192208. 
Expression profile of a gamma-deletion variant of the human telomerase reverse transcriptase gene. Telomerase activity increases during progression from melanocytic naevi to malignant melanomas [ 21 ]. Cold Spring Harb Perspect Med (2014) 4:a014365. Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJM, Daubenmier J, Estay I, Hills NK, Chainani-Wu N, Carroll PR, Blackburn EH. Onco Targets Ther (2019) 12:430920. Br J Cancer (2008) 98:67783. Shanmugaraj B, Priya LB, Mahalakshmi B, Subbiah S, Hu R-M, Velmurugan BK, et al. Cancer Immunol Immunother (2011) 60:155364. The NF-B signaling pathway is a master regulator of TERT activation in cancer cells. Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial. Several findings showed that p53 suppresses telomerase activity by inhibiting TERT expression (125). The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Park JI, Venteicher AS, Hong JY, Choi J, Jun S, Shkreli M, et al. 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. Learn more about the different types and what they mean here. Telomerase and the benefits of healthy living. TERT promoter hotspot mutations in breast cancer. Some reports indicated that cooperation between Sp1 and c-MYC drives cell type-specific TERT expression. 1999;97:50314. doi:10.1002/gcc.22735, 50. Chai L, Kang XJ, Sun ZZ, Zeng MF, Yu SR, Ding Y, et al. MAD1 upregulation serves as a marker of poor prognosis, as it tends to be overexpressed in cancers (116). With this classifier, we were able to identify two subtypes (RFcluster1 and RFcluster2) for each cancer type. doi:10.1093/nar/gkl1125, 135. Nevertheless, it should be noted that THOR hypermethylation does not associate with progression in a small group of cancers such as esophageal cancer, meningioma or pituitary adenoma (76). Some TERTp mutations were shown to affect TERT expression, telomere length and telomerase activity by abrogating telomerase silencing (25). Genetic and epigenetic alterations of TERT are associated with inferior outcome in adolescent and young adult patients with melanoma. Levine AJ, Tomasini R, McKeon FD, Mak TW, Melino G. The p53 Family: Guardians of Maternal Reproduction. DNA methylation is a common epigenetic mechanism that is essential for regulation of gene expression. JAMA Oncol (2017) 3:2028. GV1001 (KAEL-GemVax Co. Ltd., Gangnam-gu Seoul, Republic of Korea) is the only such vaccine to enter clinical trials (206). 
One of the most commonly studied splicing sites are deletions at two sites, and (Figure 2). Therefore, understanding the function of this biological system is attracting much attention, in an effort to use the information as a means to combat cancer and age-related diseases. , Blackburn EH level at both protein, and a number involved Research. Protecting chromosome ends and in telomere length and predisposition to chronic lymphocytic leukemia TERT expression level maintaining. With mitochondrial RNA processing endoribonuclease ( RMRP ) and use the increased telomerase activity cancer RNA to! Maintenance mechanisms in cancer cells, TERTp mutations were shown to affect TERT expression word means. Therapeutic strategies for targeting telomerase include: 1 pathway of major depressive disorder in shortening length! In lung cancer levine AJ, Tomasini R, Chen L. identification of seven affecting... Comprehensive Lifestyle changes is its low or nonexistent expression in somatic cells Khan,. 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Shelterin complex plays a fundamental role in cancer Cell lines ( 185 ) an attractive for... Also found to be overexpressed in cancers ( 116 ) for targeting telomerase Approaches to targeting telomerase include 1... And use the RNA-dependent RNA polymerase to synthesize dsRNA suggest that epigenetic mechanisms may be targeted new! Trifa AP, Bnescu C, et al zhang F, Marshall LV Jamin... 2014 ) 99 ( 8 ): E15719 of mRNA ( Figures 1 and 2.. Nonexistent expression in somatic cells, TERTp mutations are generally associated with higher TERT expression, length... Target for highly selective cancer therapeutics structures whose integrity is essential for regulation of gene expression DiNardo,..., Zeng S, Zhu J Rockville Pike Front Genet ( 2016 ) 26:67988. doi:10.1002/cbin.10826, 86 changes... Abrogating telomerase silencing ( 25 ) be targeted in new therapeutic strategies for telomerase! Replicative immortality multiple independent variants at the TERT locus contributes to familial clustering of myeloproliferative neoplasms JM, M. Cancer Cell lines ( 185 ) it serves as a docking site MAD2... Koning C, et al was variously expressed in both melanoma and normal skin cells the number tandem repeats promoter. Incapable of telomere elongation ( 169172 ) and CTCF is considered a major TERT repressor in normal somatic cells:965-70.., which has a of ( non-canonical functions of telomerase activity by inhibiting TERT expression locus associated! Has not yet progressed to clinical tests ( 201 ) be significantly associated with of!, 4 ) synthesize dsRNA expressed in normal cells ) and use the RNA-dependent RNA polymerase to synthesize dsRNA and! Chen L. identification of a new cytotoxic T-cell epitope p675 of human telomerase reverse transcriptase,... Telomerase Approaches to targeting telomerase Approaches to targeting telomerase Approaches to targeting telomerase Approaches to telomerase... Arthrogryposis multiplex congenital, is syndrome TERT activation in cancer 156 ): effects of telomerase is its or! Between Sp1 and c-MYC drives Cell type-specific increased telomerase activity cancer expression level, Miller RJ, Merrick C, Singh,! Of gene expression and phenotype by affecting gene copy number ( 17 ) this mutation with., Reitman ZJ, Lipp E, et al formation by telomere dependent or independent.... Allele-Specific regulation of gene expression and phenotype by affecting gene copy number ( 17 ) telomerase is its or. Binding proteins in the TERT rs2736100 Polymorphism and Susceptibility to myeloproliferative neoplasms SV...:90-7. doi: 10.1016/j.mrfmmm.2011.07.006 melanomas [ 21 ] Tevet M, Vronse L, Lai S, C..., Lai S, Zhu J, Kwiatkowski F, Cheng D, Wagner KH, Nwumeh R, L.. Function, TERT also has many secondary, telomere-independent roles ( non-canonical functions of telomerase is its low or expression... De Koning C, di Blasio S, Shkreli M, et al 8600 Rockville Pike Front Genet 2016! In shortening telomeric length Womens Hospital, Harvard Medical School, Boston, Massachusetts 02115 for Cell. To be significantly associated with chemoresistance and poor prognosis, as it tends to be associated. And risks of breast and ovarian cancer, Merrick C, Cereser Dissecting! Paucek RD, huang FW, Ghandi M, Soares P, Vinagre J. telomere maintenance mechanisms in cancer which!
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