Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
August-2021 Volume 46 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2021 Volume 46 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review)

  • Authors:
    • Zhengyi Wang
    • Xiaoying Wu
  • View Affiliations / Copyright

    Affiliations: Good Clinical Practice Center, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610071, P.R. China, Ministry of Education and Training, Chengdu Second People's Hospital, Chengdu, Sichuan 610000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 184
    |
    Published online on: July 7, 2021
       https://doi.org/10.3892/or.2021.8135
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Recent studies have found that somatic gene mutations and environmental tumor‑promoting factors are both indispensable for tumor formation. Telomeric repeat‑binding factor (TRF)2 is the core component of the telomere shelterin complex, which plays an important role in chromosome stability and the maintenance of normal cell physiological states. In recent years, TRF2 and its role in tumor formation have gradually become a research hot topic, which has promoted in‑depth discussions into tumorigenesis and treatment strategies, and has achieved promising results. Some cells bypass elimination, due to either aging, apoptosis via mutations or abnormal prolongation of the mitotic cycle, and enter the telomere crisis period, where large‑scale DNA reorganization occurs repeatedly, which manifests as the precancerous cell cycle. Finally, at the end of the crisis cycle, the mutation activates either the expression level of telomerase or activates the alternative lengthening of telomere mechanism to extend the local telomeres. Under the protection of TRF2, chromosomes are gradually stabilized, immortal cells are formed and the stagewise mutation‑driven transformation of normal cells to cancer cells is completed. In addition, TRF2 also shares the characteristics of environmental tumor‑promoting factors. It acts on multiple signal transduction pathway‑related proteins associated with cell proliferation, and affects peripheral angiogenesis, inhibits the immune recognition and killing ability of the microenvironment, and maintains the stemness characteristics of tumor cells. TRF2 levels are abnormally elevated by a variety of tumor control proteins, which are more conducive to the protection of telomeres and the survival of tumor cells. In brief, the various regulatory mechanisms which tumor cells rely on to survive are organically integrated around TRF2, forming a regulatory network, which is conducive to the optimization of the survival direction of heterogeneous tumor cells, and promotes their survival and adaptability. In terms of clinical application, TRF2 is expected to become a new type of cancer prognostic marker and a new tumor treatment target. Inhibition of TRF2 overexpression could effectively cut off the core network regulating tumor cell survival, reduce drug resistance, or bypass the mutation under the pressure of tumor treatment selection, which may represent a promising therapeutic strategy for the complete eradication of tumors in the clinical setting. Based on recent research, the aim of the present review was to systematically elaborate on the basic structure and functional characteristics of TRF2 and its role in tumor formation, and to analyze the findings indicating that TRF2 deficiency or overexpression could cause severe damage to telomere function and telomere shortening, and induce DNA damage response and chromosomal instability.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Martincorena I, Fowler JC, Wabik A, Lawson ARJ, Abascal F, Hall MWJ, Cagan A, Murai K, Mahbubani K, Stratton MR, et al: Somatic mutant clones colonize the human esophagus with age. Science. 362:911–917. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Yokoyama A, Kakiuchi N, Yoshizato T, Nannya Y, Suzuki H, Takeuchi Y, Shiozawa Y, Sato Y, Aoki K, Kim SK, et al: Age-related remodelling of oesophageal epithelia by mutated cancer drivers. Nature. 565:312–317. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Goerttler K, Loehrke H, Schweizer J and Hesse B: Two-stage skin carcinogenesis by systemic initiation of pregnant mice with 7,12-dimethylbenz(a)anthracene during gestation days 6–20 and postnatal promotion of the F 1-generation with the phorbol ester 12-tetradecanoylphorbol-13-acetate. J Cancer Res Clin Oncol. 98:267–275. 1980. View Article : Google Scholar : PubMed/NCBI

4 

Goerttler K, Loehrke H, Hesse B, Milz A and Schweizer J: Diaplacental initiation of NMRI mice with 7,12-dimethylbenz[a]anthracene during gestation days 6–20 and postnatal treatment of the F1-generation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate: Tumor incidence in organs other than the skin. Carcinogenesis. 2:1087–1094. 1981. View Article : Google Scholar : PubMed/NCBI

5 

Fairall L, Chapman L, Moss H, de Lange T and Rhodes D: Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2. Mol Cell. 8:351–361. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Mondello C, Smirnova A and Giulotto E: Gene amplification, radiation sensitivity and DNA double-strand breaks. Mutat Res. 704:29–37. 2010. View Article : Google Scholar : PubMed/NCBI

7 

El Maï M, Wagner KD, Michiels JF, Ambrosetti D, Borderie A, Destree S, Renault V, Djerbi N, Giraud-Panis MJ, Gilson E and Wagner N: The telomeric protein TRF2 regulates angiogenesis by binding and activating the PDGFRβ promoter. Cell Rep. 9:1047–1060. 2014. View Article : Google Scholar

8 

Biroccio A, Cherfils-Vicini J, Augereau A, Pinte S, Bauwens S, Ye J, Simonet T, Horard B, Jamet K, Cervera L, et al: TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells. Nat Cell Biol. 15:818–828. 2013. View Article : Google Scholar : PubMed/NCBI

9 

van Steensel B, Smogorzewska A and de Lange T: TRF2 protects human telomeres from end-to-end fusions. Cell. 92:401–413. 1998. View Article : Google Scholar : PubMed/NCBI

10 

de Lange T: Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 19:2100–2110. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Smith EM, Pendlebury DF and Nandakumar J: Structural biology of telomeres and telomerase. Cell Mol Life Sci. 77:61–79. 2020. View Article : Google Scholar : PubMed/NCBI

12 

Deng Z, Norseen J, Wiedmer A, Riethman H and Lieberman PM: TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell. 35:403–413. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Necasová I, Janoušková E, Klumpler T and Hofr C: Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it. Nucleic Acids Res. 45:12170–12180. 2017. View Article : Google Scholar

14 

O'Connor MS, Safari A, Xin H, Liu D and Songyang Z: A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci USA. 103:11874–11879. 2006. View Article : Google Scholar

15 

Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, O'Connor MS and Songyang Z: TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature. 445:559–562. 2007. View Article : Google Scholar : PubMed/NCBI

16 

van Overbeek M and de Lange T: Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase. Curr Biol. 16:1295–1302. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Lenain C, Bauwens S, Amiard S, Brunori M, Giraud-Panis MJ and Gilson E: The Apollo 5′exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol. 16:1303–1310. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Kim H, Lee OH, Xin H, Chen LY, Qin J, Chae HK, Lin SY, Safari A, Liu D and Songyang Z: TRF2 functions as a protein hub and regulates telomere maintenance by recognizing specific peptide motifs. Nat Struct Mol Biol. 16:372–379. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Benarroch-Popivker D, Pisano S, Mendez-Bermudez A, Lototska L, Kaur P, Bauwens S, Djerbi N, Latrick CM, Fraisier V, Pei B, et al: TRF2-mediated control of telomere DNA topology as a mechanism for chromosome-end protection. Mol Cell. 61:274–286. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Giraud-Panis MJ, Pisano S, Benarroch-Popivker D, Pei B, Le Du MH and Gilson E: One identity or more for telomeres? Front Oncol. 3:482013. View Article : Google Scholar : PubMed/NCBI

21 

Broccoli D, Smogorzewska A, Chong L and de Lange T: Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 17:231–235. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Baker AM, Fu Q, Hayward W, Lindsay SM and Fletcher TM: The Myb/SANT domain of the telomere-binding protein TRF2 alters chromatin structure. Nucleic Acids Res. 37:5019–5031. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Bilaud T, Brun C, Ancelin K, Koering CE, Laroche T and Gilson E: Telomeric localization of TRF2, a novel human telobox protein. Nat Genet. 17:236–239. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Denchi EL and de Lange T: Protection of telomeres through independent control of ATM and ATR by TRF2 and POT1. Nature. 448:1068–1071. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Gilson E and Géli V: How telomeres are replicated. Nat Rev Mol Cell Biol. 8:825–838. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Ye J, Lenain C, Bauwens S, Rizzo A, Saint-Léger A, Poulet A, Benarroch D, Magdinier F, Morere J, Amiard S, et al: TRF2 and apollo cooperate with topoisomerase 2alpha to protect human telomeres from replicative damage. Cell. 142:230–242. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Greider CW: Telomeres do D-loop-T-loop. Cell. 97:419–422. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H and de Lange T: Mammalian telomeres end in a large duplex loop. Cell. 97:503–514. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Timashev LA and De Lange T: Characterization of t-loop formation by TRF2. Nucleus. 11:164–177. 2020. View Article : Google Scholar : PubMed/NCBI

30 

Feuerhahn S, Chen LY, Luke B and Porro A: No DDRama at chromosome ends: TRF2 takes centre stage. Trends Biochem Sci. 40:275–285. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Schmutz I, Timashev L, Xie W, Patel DJ and de Lange T: TRF2 binds branched DNA to safeguard telomere integrity. Nat Struct Mol Biol. 24:734–742. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Sarek G, Kotsantis P, Ruis P, Van Ly D, Margalef P, Borel V, Zheng XF, Flynn HR, Snijders AP, Chowdhury D, et al: CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle. Nature. 575:523–527. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Sarek G, Vannier JB, Panier S, Petrini JHJ and Boulton SJ: TRF2 Recruits RTEL1 to Telomeres in S Phase to Promote T-Loop Unwinding. Mol Cell. 61:788–789. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Bower BD and Griffith JD: TRF1 and TRF2 differentially modulate Rad51-mediated telomeric and nontelomeric displacement loop formation in vitro. Biochemistry. 53:5485–5495. 2014. View Article : Google Scholar : PubMed/NCBI

35 

d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP and Jackson SP: A DNA damage checkpoint response in telomere-initiated senescence. Nature. 426:194–198. 2003. View Article : Google Scholar

36 

Takai H, Smogorzewska A and de Lange T: DNA damage foci at dysfunctional telomeres. Curr Biol. 13:1549–1556. 2003. View Article : Google Scholar : PubMed/NCBI

37 

Okamoto K, Bartocci C, Ouzounov I, Diedrich JK, Yates JR III and Denchi EL: A two-step mechanism for TRF2-mediated chromosome-end protection. Nature. 494:502–505. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Frescas D and de Lange T: TRF2-tethered TIN2 can mediate telomere protection by TPP1/POT1. Mol Cell Biol. 34:1349–1362. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Takai KK, Kibe T, Donigian JR, Frescas D and de Lange T: Telomere protection by TPP1/POT1 requires tethering to TIN2. Mol Cell. 67:1622017. View Article : Google Scholar : PubMed/NCBI

40 

Fuchs E: The tortoise and the hair: Slow-cycling cells in the stem cell race. Cell. 137:811–819. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Opresko PL, von Kobbe C, Laine JP, Harrigan J, Hickson ID and Bohr VA: Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem. 277:41110–41119. 2002. View Article : Google Scholar : PubMed/NCBI

42 

Stavropoulos DJ, Bradshaw PS, Li X, Pasic I, Truong K, Ikura M, Ungrin M and Meyn MS: The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis. Hum Mol Genet. 11:3135–3144. 2002. View Article : Google Scholar : PubMed/NCBI

43 

Rothkamm K, Krüger I, Thompson LH and Löbrich M: Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 23:5706–5715. 2003. View Article : Google Scholar : PubMed/NCBI

44 

Mladenov E and Iliakis G: Induction and repair of DNA double strand breaks: The increasing spectrum of non-homologous end joining pathways. Mutat Res. 711:61–72. 2011. View Article : Google Scholar : PubMed/NCBI

45 

Ribes-Zamora A, Indiviglio SM, Mihalek I, Williams CL and Bertuch AA: TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres. Cell Rep. 5:194–206. 2013. View Article : Google Scholar : PubMed/NCBI

46 

Dimitrova N, Chen YC, Spector DL and de Lange T: 53BP1 promotes non-homologous end joining of telomeres by increasing chromatin mobility. Nature. 456:524–528. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Mirman Z, Lottersberger F, Takai H, Kibe T, Gong Y, Takai K, Bianchi A, Zimmermann M, Durocher D and de Lange T: 53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in. Nature. 560:112–116. 2018. View Article : Google Scholar : PubMed/NCBI

48 

Timashev LA, Babcock H, Zhuang X and de Lange T: The DDR at telomeres lacking intact shelterin does not require substantial chromatin decompaction. Genes Dev. 31:578–589. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Blasco MA: Telomeres and human disease: Ageing, cancer and beyond. Nat Rev Genet. 6:611–622. 2005. View Article : Google Scholar : PubMed/NCBI

50 

Sfeir A and de Lange T: Removal of shelterin reveals the telomere end-protection problem. Science. 336:593–597. 2012. View Article : Google Scholar : PubMed/NCBI

51 

Celli GB, Denchi EL and de Lange T: Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination. Nat Cell Biol. 8:885–890. 2006. View Article : Google Scholar : PubMed/NCBI

52 

Kibe T, Osawa GA, Keegan CE and de Lange T: Telomere protection by TPP1 is mediated by POT1a and POT1b. Mol Cell Biol. 30:1059–1066. 2010. View Article : Google Scholar : PubMed/NCBI

53 

Shamanna RA, Lu H, de Freitas JK, Tian J, Croteau DL and Bohr VA: WRN regulates pathway choice between classical and alternative non-homologous end joining. Nat Commun. 7:137852016. View Article : Google Scholar : PubMed/NCBI

54 

Fallet E, Jolivet P, Soudet J, Lisby M, Gilson E and Teixeira MT: Length-dependent processing of telomeres in the absence of telomerase. Nucleic Acids Res. 42:3648–3665. 2014. View Article : Google Scholar : PubMed/NCBI

55 

Wu L, Multani AS, He H, Cosme-Blanco W, Deng Y, Deng JM, Bachilo O, Pathak S, Tahara H, Bailey SM, et al: Pot1 deficiency initiates DNA damage checkpoint activation and aberrant homologous recombination at telomeres. Cell. 126:49–62. 2006. View Article : Google Scholar : PubMed/NCBI

56 

Rai R, Chen Y, Lei M and Chang S: TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nat Commun. 7:108812016. View Article : Google Scholar : PubMed/NCBI

57 

González-Prieto R, Cuijpers SA, Luijsterburg MS, van Attikum H and Vertegaal AC: SUMOylation and PARylation cooperate to recruit and stabilize SLX4 at DNA damage sites. EMBO Rep. 16:512–519. 2015. View Article : Google Scholar

58 

Capper R, Britt-Compton B, Tankimanova M, Rowson J, Letsolo B, Man S, Haughton M and Baird DM: The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes Dev. 21:2495–2508. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Karlseder J, Smogorzewska A and de Lange T: Senescence induced by altered telomere state, not telomere loss. Science. 295:2446–2449. 2002. View Article : Google Scholar : PubMed/NCBI

60 

Smogorzewska A, van Steensel B, Bianchi A, Oelmann S, Schaefer MR, Schnapp G and de Lange T: Control of human telomere length by TRF1 and TRF2. Mol Cell Biol. 20:1659–1668. 2000. View Article : Google Scholar : PubMed/NCBI

61 

Muñoz P, Blanco R and Blasco MA: Role of the TRF2 telomeric protein in cancer and ageing. Cell Cycle. 5:718–721. 2006. View Article : Google Scholar

62 

Saint-Léger A, Koelblen M, Civitelli L, Bah A, Djerbi N, Giraud-Panis MJ, Londoño-Vallejo A, Ascenzioni F and Gilson E: The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres. Cell Cycle. 13:2469–2474. 2014. View Article : Google Scholar

63 

Wilson JS, Tejera AM, Castor D, Toth R, Blasco MA and Rouse J: Localization-dependent and -independent roles of SLX4 in regulating telomeres. Cell Rep. 4:853–860. 2013. View Article : Google Scholar : PubMed/NCBI

64 

Wu Y, Zacal NJ, Rainbow AJ and Zhu XD: XPF with mutations in its conserved nuclease domain is defective in DNA repair but functions in TRF2-mediated telomere shortening. DNA Repair (Amst). 6:157–166. 2007. View Article : Google Scholar : PubMed/NCBI

65 

Wu Y, Mitchell TR and Zhu XD: Human XPF controls TRF2 and telomere length maintenance through distinctive mechanisms. Mech Ageing Dev. 129:602–610. 2008. View Article : Google Scholar : PubMed/NCBI

66 

Menendez JA, Rubio MA, Campisi J and Lupu R: Heregulin, a new regulator of telomere length in human cells. Oncotarget. 6:39422–39436. 2015. View Article : Google Scholar : PubMed/NCBI

67 

Menendez JA, Benboudjema L, Vellon L, Rubio MA, Espinoza I, Campisi J and Lupu R: Heregulin, a new interactor of the telosome/shelterin complex in human telomeres. Oncotarget. 6:39408–39421. 2015. View Article : Google Scholar : PubMed/NCBI

68 

Baur JA, Zou Y, Shay JW and Wright WE: Telomere position effect in human cells. Science. 292:2075–2077. 2001. View Article : Google Scholar : PubMed/NCBI

69 

Kim W, Ludlow AT, Min J, Robin JD, Stadler G, Mender I, Lai TP, Zhang N, Wright WE and Shay JW: Regulation of the human telomerase gene TERT by telomere position effect-over long distances (TPE-OLD): Implications for aging and cancer. PLoS Biol. 14:e20000162016. View Article : Google Scholar : PubMed/NCBI

70 

Mukherjee AK, Sharma S, Bagri S, Kutum R, Kumar P, Hussain A, Singh P, Saha D, Kar A, Dash D and Chowdhury S: Telomere repeat-binding factor 2 binds extensively to extra-telomeric G-quadruplexes and regulates the epigenetic status of several gene promoters. J Biol Chem. 294:17709–17722. 2019. View Article : Google Scholar : PubMed/NCBI

71 

Bradshaw PS, Stavropoulos DJ and Meyn MS: Human telomeric protein TRF2 associates with genomic double-strand breaks as an early response to DNA damage. Nat Genet. 37:193–197. 2005. View Article : Google Scholar : PubMed/NCBI

72 

Hussain T, Saha D, Purohit G, Kar A, Kishore Mukherjee A, Sharma S, Sengupta S, Dhapola P, Maji B, Vedagopuram S, et al: Transcription regulation of CDKN1A (p21/CIP1/WAF1) by TRF2 is epigenetically controlled through the REST repressor complex. Sci Rep. 7:115412017. View Article : Google Scholar : PubMed/NCBI

73 

Purohit G, Mukherjee AK, Sharma S and Chowdhury S: Extratelomeric binding of the telomere binding protein TRF2 at the PCGF3 promoter is G-Quadruplex Motif-dependent. Biochemistry. 57:2317–2324. 2018. View Article : Google Scholar : PubMed/NCBI

74 

Williamson JR, Raghuraman MK and Cech TR: Monovalent cation-induced structure of telomeric DNA: The G-quartet model. Cell. 59:871–880. 1989. View Article : Google Scholar : PubMed/NCBI

75 

Phan AT: Human telomeric G-quadruplex: Structures of DNA and RNA sequences. FEBS J. 277:1107–1117. 2010. View Article : Google Scholar : PubMed/NCBI

76 

Muniyappa K and Kironmai KM: Telomere structure, replication and length maintenance. Crit Rev Biochem Mol Biol. 33:297–336. 1998. View Article : Google Scholar : PubMed/NCBI

77 

Luu KN, Phan AT, Kuryavyi V, Lacroix L and Patel DJ: Structure of the human telomere in K+ solution: An intramolecular (3 + 1) G-quadruplex scaffold. J Am Chem Soc. 128:9963–9970. 2006. View Article : Google Scholar : PubMed/NCBI

78 

Brázda V, Hároníková L, Liao JC and Fojta M: DNA and RNA quadruplex-binding proteins. Int J Mol Sci. 15:17493–17517. 2014. View Article : Google Scholar

79 

Pedroso IM, Hayward W and Fletcher TM: The effect of the TRF2 N-terminal and TRFH regions on telomeric G-quadruplex structures. Nucleic Acids Res. 37:1541–1554. 2009. View Article : Google Scholar : PubMed/NCBI

80 

Rawal P, Kummarasetti VB, Ravindran J, Kumar N, Halder K, Sharma R, Mukerji M, Das SK and Chowdhury S: Genome-wide prediction of G4 DNA as regulatory motifs: Role in Escherichia coli global regulation. Genome Res. 16:644–655. 2006. View Article : Google Scholar : PubMed/NCBI

81 

Sengupta A, Roy SS and Chowdhury S: Non-duplex G-Quadruplex DNA Structure: A developing story from predicted sequences to DNA structure-dependent epigenetics and beyond. Acc Chem Res. 54:46–56. 2021. View Article : Google Scholar : PubMed/NCBI

82 

Killela PJ, Pirozzi CJ, Healy P, Reitman ZJ, Lipp E, Rasheed BA, Yang R, Diplas BH, Wang Z, Greer PK, et al: Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget. 5:1515–1525. 2014. View Article : Google Scholar : PubMed/NCBI

83 

Heidenreich B, Nagore E, Rachakonda PS, Garcia-Casado Z, Requena C, Traves V, Becker J, Soufir N, Hemminki K and Kumar R: Telomerase reverse transcriptase promoter mutations in primary cutaneous melanoma. Nat Commun. 5:34012014. View Article : Google Scholar : PubMed/NCBI

84 

Pinyol R, Tovar V and Llovet JM: TERT promoter mutations: Gatekeeper and driver of hepatocellular carcinoma. J Hepatol. 61:685–687. 2014. View Article : Google Scholar : PubMed/NCBI

85 

Rachakonda PS, Hosen I, de Verdier PJ, Fallah M, Heidenreich B, Ryk C, Wiklund NP, Steineck G, Schadendorf D, Hemminki K and Kumar R: TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism. Proc Natl Acad Sci USA. 110:17426–17431. 2013. View Article : Google Scholar : PubMed/NCBI

86 

Thakur RK, Kumar P, Halder K, Verma A, Kar A, Parent JL, Basundra R, Kumar A and Chowdhury S: Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression. Nucleic Acids Res. 37:172–183. 2009. View Article : Google Scholar : PubMed/NCBI

87 

Paramasivam M, Membrino A, Cogoi S, Fukuda H, Nakagama H and Xodo LE: Protein hnRNP A1 and its derivative Up1 unfold quadruplex DNA in the human KRAS promoter: Implications for transcription. Nucleic Acids Res. 37:2841–2853. 2009. View Article : Google Scholar : PubMed/NCBI

88 

Cogoi S, Paramasivam M, Membrino A, Yokoyama KK and Xodo LE: The KRAS promoter responds to Myc-associated zinc finger and poly(ADP-ribose) polymerase 1 proteins, which recognize a critical quadruplex-forming GA-element. J Biol Chem. 285:22003–22016. 2010. View Article : Google Scholar : PubMed/NCBI

89 

Yadav VK, Abraham JK, Mani P, Kulshrestha R and Chowdhury S: QuadBase: Genome-wide database of G4 DNA-occurrence and conservation in human, chimpanzee, mouse and rat promoters and 146 microbes. Nucleic Acids Res. 36:D381–D385. 2008. View Article : Google Scholar : PubMed/NCBI

90 

Mukherjee AK, Sharma S, Sengupta S, Saha D, Kumar P, Hussain T, Srivastava V, Roy SD, Shay JW and Chowdhury S: Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends. PLoS Genet. 14:e10077822018. View Article : Google Scholar : PubMed/NCBI

91 

Shay JW and Wright WE: Telomeres and telomerase: Three decades of progress. Nat Rev Genet. 20:299–309. 2019. View Article : Google Scholar : PubMed/NCBI

92 

Rajagopalan H and Lengauer C: CIN-ful cancers. Cancer Chemother Pharmacol. 54 (Suppl 1):S65–S68. 2004.PubMed/NCBI

93 

Tlsty TD: Genomic instability and its role in neoplasia. Curr Top Microbiol Immunol. 221:37–46. 1997.PubMed/NCBI

94 

Lengauer C, Kinzler KW and Vogelstein B: Genetic instabilities in human cancers. Nature. 396:643–649. 1998. View Article : Google Scholar : PubMed/NCBI

95 

Palm W and de Lange T: How shelterin protects mammalian telomeres. Annu Rev Genet. 42:301–334. 2008. View Article : Google Scholar : PubMed/NCBI

96 

Wright WE, Pereira-Smith OM and Shay JW: Reversible cellular senescence: Implications for immortalization of normal human diploid fibroblasts. Mol Cell Biol. 9:3088–3092. 1989. View Article : Google Scholar : PubMed/NCBI

97 

O'Hagan RC, Chang S, Maser RS, Mohan R, Artandi SE, Chin L and DePinho RA: Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell. 2:149–155. 2002. View Article : Google Scholar

98 

Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D, Kaplunov JM, Bucci G, Dobreva M, Matti V, Beausejour CM, et al: Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol. 14:355–365. 2012. View Article : Google Scholar : PubMed/NCBI

99 

Feldser DM and Greider CW: Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 11:461–469. 2007. View Article : Google Scholar : PubMed/NCBI

100 

Counter CM, Avilion AA, LeFeuvre CE, Stewart NG, Greider CW, Harley CB and Bacchetti S: Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11:1921–1929. 1992. View Article : Google Scholar : PubMed/NCBI

101 

Hayashi MT, Cesare AJ, Rivera T and Karlseder J: Cell death during crisis is mediated by mitotic telomere deprotection. Nature. 522:492–496. 2015. View Article : Google Scholar : PubMed/NCBI

102 

Sabatier L, Ricoul M, Pottier G and Murnane JP: The loss of a single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol Cancer Res. 3:139–150. 2005. View Article : Google Scholar : PubMed/NCBI

103 

Bailey SM and Murnane JP: Telomeres, chromosome instability and cancer. Nucleic Acids Res. 34:2408–2417. 2006. View Article : Google Scholar : PubMed/NCBI

104 

Maciejowski J and de Lange T: Telomeres in cancer: Tumour suppression and genome instability. Nat Rev Mol Cell Biol. 18:175–186. 2017. View Article : Google Scholar : PubMed/NCBI

105 

Martínez P and Blasco MA: Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 216:875–887. 2017. View Article : Google Scholar

106 

Murnane JP and Sabatier L: Chromosome rearrangements resulting from telomere dysfunction and their role in cancer. Bioessays. 26:1164–1174. 2004. View Article : Google Scholar : PubMed/NCBI

107 

Giraud-Panis MJ, Pisano S, Poulet A, Le Du MH and Gilson E: Structural identity of telomeric complexes. FEBS Lett. 584:3785–3799. 2010. View Article : Google Scholar : PubMed/NCBI

108 

Salhab M, Jiang WG, Newbold RF and Mokbel K: The expression of gene transcripts of telomere-associated genes in human breast cancer: Correlation with clinico-pathological parameters and clinical outcome. Breast Cancer Res Treat. 109:35–46. 2008. View Article : Google Scholar : PubMed/NCBI

109 

Pascua I, Fernández-Marcelo T, Sánchez-Pernaute A, de Juan C, Head J, Torres-García AJ and Iniesta P: Prognostic value of telomere function in gastric cancers with and without microsatellite instability. Eur J Gastroenterol Hepatol. 27:162–169. 2015. View Article : Google Scholar : PubMed/NCBI

110 

Yamada K, Yagihashi A, Yamada M, Asanuma K, Moriai R, Kobayashi D, Tsuji N and Watanabe N: Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells. Anticancer Res. 22:1315–1320. 2002.PubMed/NCBI

111 

Su CH, Cheng C, Tzeng TY, Lin IH and Hsu MT: An H2A Histone Isotype, H2ac, associates with telomere and maintains telomere integrity. PLoS One. 11:e01563782016. View Article : Google Scholar : PubMed/NCBI

112 

Bojovic B, Ho HY, Wu J and Crowe DL: Stem cell expansion during carcinogenesis in stem cell-depleted conditional telomeric repeat factor 2 null mutant mice. Oncogene. 32:5156–5166. 2013. View Article : Google Scholar : PubMed/NCBI

113 

Lagunas AM, Wu J and Crowe DL: Telomere DNA damage signaling regulates cancer stem cell evolution, epithelial mesenchymal transition, and metastasis. Oncotarget. 8:80139–80155. 2017. View Article : Google Scholar : PubMed/NCBI

114 

Rossi DJ, Jamieson CH and Weissman IL: Stems cells and the pathways to aging and cancer. Cell. 132:681–696. 2008. View Article : Google Scholar : PubMed/NCBI

115 

Singh A and Settleman J: EMT, cancer stem cells and drug resistance: An emerging axis of evil in the war on cancer. Oncogene. 29:4741–4751. 2010. View Article : Google Scholar : PubMed/NCBI

116 

Härle-Bachor C and Boukamp P: Telomerase activity in the regenerative basal layer of the epidermis inhuman skin and in immortal and carcinoma-derived skin keratinocytes. Proc Natl Acad Sci USA. 93:6476–6481. 1996. View Article : Google Scholar

117 

González-Suárez E, Samper E, Ramírez A, Flores JM, Martín-Caballero J, Jorcano JL and Blasco MA: Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J. 20:2619–2630. 2001. View Article : Google Scholar

118 

Blanco R, Muñoz P, Flores JM, Klatt P and Blasco MA: Telomerase abrogation dramatically accelerates TRF2-induced epithelial carcinogenesis. Genes Dev. 21:206–220. 2007. View Article : Google Scholar : PubMed/NCBI

119 

Matsutani N, Yokozaki H and Tahara E, Tahara H, Kuniyasu H, Haruma K, Chayama K, Yasui W and Tahara E: Expression of telomeric repeat binding factor 1 and 2 and TRF1-interacting nuclear protein 2 in human gastric carcinomas. Int J Oncol. 19:507–512. 2001.PubMed/NCBI

120 

Oh BK, Kim YJ, Park C and Park YN: Up-regulation of telomere-binding proteins, TRF1, TRF2, and TIN2 is related to telomere shortening during human multistep hepatocarcinogenesis. Am J Pathol. 166:73–80. 2005. View Article : Google Scholar : PubMed/NCBI

121 

Xu L and Blackburn EH: Human cancer cells harbor T-stumps, a distinct class of extremely short telomeres. Mol Cell. 28:315–327. 2007. View Article : Google Scholar : PubMed/NCBI

122 

Muñoz P, Blanco R, Flores JM and Blasco MA: XPF nuclease-dependent telomere loss and increased DNA damage in mice overexpressing TRF2 result in premature aging and cancer. Nat Genet. 37:1063–1071. 2005. View Article : Google Scholar

123 

Nera B, Huang HS, Lai T and Xu L: Elevated levels of TRF2 induce telomeric ultrafine anaphase bridges and rapid telomere deletions. Nat Commun. 6:101322015. View Article : Google Scholar : PubMed/NCBI

124 

Rai R, Zheng H, He H, Luo Y, Multani A, Carpenter PB and Chang S: The function of classical and alternative non-homologous end-joining pathways in the fusion of dysfunctional telomeres. EMBO J. 29:2598–2610. 2010. View Article : Google Scholar : PubMed/NCBI

125 

Dong W, Shen R, Wang Q, Gao Y, Qi X, Jiang H, Yao J, Lin X, Wu Y and Wang L: Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells. Cancer Biol Ther. 8:2166–2174. 2009. View Article : Google Scholar : PubMed/NCBI

126 

Raynaud CM, Jang SJ, Nuciforo P, Lantuejoul S, Brambilla E, Mounier N, Olaussen KA, André F, Morat L, Sabatier L and Soria JC: Telomere shortening is correlated with the DNA damage response and telomeric protein down-regulation in colorectal preneoplastic lesions. Ann Oncol. 19:1875–1881. 2008. View Article : Google Scholar : PubMed/NCBI

127 

Brummelkamp TR, Bernards R and Agami R: A system for stable expression of short interfering RNAs in mammalian cells. Science. 296:550–553. 2002. View Article : Google Scholar : PubMed/NCBI

128 

Gartel AL, Goufman E, Najmabadi F and Tyner AL: Sp1 and Sp3 activate p21 (WAF1/CIP1) gene transcription in the Caco-2 colon adenocarcinoma cell line. Oncogene. 19:5182–5188. 2000. View Article : Google Scholar : PubMed/NCBI

129 

Takami Y, Russell MB, Gao C, Mi Z, Guo H, Mantyh CR and Kuo PC: Sp1 regulates osteopontin expression in SW480 human colon adenocarcinoma cells. Surgery. 142:163–169. 2007. View Article : Google Scholar : PubMed/NCBI

130 

Zhu GH, Lenzi M and Schwartz EL: The Sp1 transcription factor contributes to the tumor necrosis factor-induced expression of the angiogenic factor thymidine phosphorylase in human colon carcinoma cells. Oncogene. 21:8477–8485. 2002. View Article : Google Scholar : PubMed/NCBI

131 

Diala I, Wagner N, Magdinier F, Shkreli M, Sirakov M, Bauwens S, Schluth-Bolard C, Simonet T, Renault VM, Ye J, et al: Telomere protection and TRF2 expression are enhanced by the canonical Wnt signalling pathway. EMBO Rep. 14:356–363. 2013. View Article : Google Scholar : PubMed/NCBI

132 

Wu S, Ge Y, Li X, Yang Y, Zhou H, Lin K, Zhang Z and Zhao Y: BRM-SWI/SNF chromatin remodeling complex enables functional telomeres by promoting co-expression of TRF2 and TRF1. PLoS Genet. 16:e10087992020. View Article : Google Scholar : PubMed/NCBI

133 

Dong W, Wang L, Chen X, Sun P and Wu Y: Upregulation and CpG island hypomethylation of the TRF2 gene in human gastric cancer. Dig Dis Sci. 55:997–1003. 2010. View Article : Google Scholar : PubMed/NCBI

134 

Luo Z, Feng X, Wang H, Xu W, Zhao Y, Ma W, Jiang S, Liu D, Huang J and Songyang Z: Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression. Aging Cell. 14:391–399. 2015. View Article : Google Scholar : PubMed/NCBI

135 

Dinami R, Ercolani C, Petti E, Piazza S, Ciani Y, Sestito R, Sacconi A, Biagioni F, le Sage C, Agami R, et al: miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res. 74:4145–4156. 2014. View Article : Google Scholar : PubMed/NCBI

136 

Dinami R, Porru M, Amoreo CA, Sperduti I, Mottolese M, Buglioni S, Marinelli D, Maugeri-Saccà M, Sacconi A, Blandino G, et al: TRF2 and VEGF-A: An unknown relationship with prognostic impact on survival of colorectal cancer patients. J Exp Clin Cancer Res. 39:1112020. View Article : Google Scholar : PubMed/NCBI

137 

Zizza P, Dinami R, Porru M, Cingolani C, Salvati E, Rizzo A, D'Angelo C, Petti E, Amoreo CA, Mottolese M, et al: TRF2 positively regulates SULF2 expression increasing VEGF-A release and activity in tumor microenvironment. Nucleic Acids Res. 47:3365–3382. 2019. View Article : Google Scholar : PubMed/NCBI

138 

Gavert N and Ben-Ze'ev A: Beta-Catenin signaling in biological control and cancer. J Cell Biochem. 102:820–828. 2007. View Article : Google Scholar : PubMed/NCBI

139 

Dhillon AS, Hagan S, Rath O and Kolch W: MAP kinase signalling pathways in cancer. Oncogene. 26:3279–3290. 2007. View Article : Google Scholar : PubMed/NCBI

140 

Jones SM and Kazlauskas A: Growth factor-dependent signaling and cell cycle progression. FEBS Lett. 490:110–116. 2001. View Article : Google Scholar : PubMed/NCBI

141 

Roberts EC, Shapiro PS, Nahreini TS, Pages G, Pouyssegur J and Ahn NG: Distinct cell cycle timing requirements for extracellular signal-regulated kinase and phosphoinositide 3-kinase signaling pathways in somatic cell mitosis. Mol Cell Biol. 22:7226–7241. 2002. View Article : Google Scholar : PubMed/NCBI

142 

Nijjar T, Bassett E, Garbe J, Takenaka Y, Stampfer MR, Gilley D and Yaswen P: Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells. Oncogene. 24:3369–3376. 2005. View Article : Google Scholar : PubMed/NCBI

143 

Picco V, Coste I, Giraud-Panis MJ, Renno T, Gilson E and Pagès G: ERK1/2/MAPK pathway-dependent regulation of the telomeric factor TRF2. Oncotarget. 7:46615–46627. 2016. View Article : Google Scholar : PubMed/NCBI

144 

Shukla S, Kanwal R, Shankar E, Datt M, Chance MR, Fu P, MacLennan GT and Gupta S: Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget. 6:31216–31232. 2015. View Article : Google Scholar : PubMed/NCBI

145 

Li T, Wong VK, Jiang ZH, Jiang SP, Liu Y, Wang TY, Yao XJ, Su XH, Yan FG, Liu J, et al: Mutation of cysteine 46 in IKK-beta increases inflammatory responses. Oncotarget. 6:31805–31819. 2015. View Article : Google Scholar : PubMed/NCBI

146 

An J, Wu M, Xin X, Lin Z, Li X, Zheng Q, Gui X, Li T, Pu H, Li H and Lu D: Inflammatory related gene IKKα, IKKβ, IKKγ cooperates to determine liver cancer stem cells progression by altering telomere via heterochromatin protein 1-HOTAIR axis. Oncotarget. 7:50131–50149. 2016. View Article : Google Scholar : PubMed/NCBI

147 

Baskar R, Dai J, Wenlong N, Yeo R and Yeoh KW: Biological response of cancer cells to radiation treatment. Front Mol Biosci. 1:242014. View Article : Google Scholar : PubMed/NCBI

148 

Saha A, Shree Padhi S, Roy S and Banerjee B: HCT116 colonospheres shows elevated expression of hTERT and β-catenin protein-a short report. J Stem Cells. 9:243–251. 2014.PubMed/NCBI

149 

Saha A, Roy S, Kar M, Roy S, Thakur S, Padhi S, Akhter Y and Banerjee B: Role of telomeric TRF2 in orosphere formation and CSC phenotype maintenance through efficient DNA repair pathway and its correlation with recurrence in OSCC. Stem Cell Rev Rep. 14:871–887. 2018. View Article : Google Scholar : PubMed/NCBI

150 

Janoušková E, Nečasová I, Pavloušková J, Zimmermann M, Hluchý M, Marini V, Nováková M and Hofr C: Human Rap1 modulates TRF2 attraction to telomeric DNA. Nucleic Acids Res. 43:2691–2700. 2015. View Article : Google Scholar

151 

Anuja K, Chowdhury AR, Saha A, Roy S, Rath AK, Kar M and Banerjee B: Radiation-induced DNA damage response and resistance in colorectal cancer stem-like cells. Int J Radiat Biol. 95:667–679. 2019. View Article : Google Scholar : PubMed/NCBI

152 

Osterwald S, Deeg KI, Chung I, Parisotto D, Wörz S, Rohr K, Erfle H and Rippe K: PML induces compaction, TRF2 depletion and DNA damage signaling at telomeres and promotes their alternative lengthening. J Cell Sci. 128:1887–1900. 2015. View Article : Google Scholar : PubMed/NCBI

153 

Zhang P, Pazin MJ, Schwartz CM, Becker KG, Wersto RP, Dilley CM and Mattson MP: Nontelomeric TRF2-REST interaction modulates neuronal gene silencing and fate of tumor and stem cells. Curr Biol. 18:1489–1494. 2008. View Article : Google Scholar : PubMed/NCBI

154 

Preusser M, de Ribaupierre S, Wöhrer A, Erridge SC, Hegi M, Weller M and Stupp R: Current concepts and management of glioblastoma. Ann Neurol. 70:9–21. 2011. View Article : Google Scholar : PubMed/NCBI

155 

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD and Rich JN: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI

156 

Bai Y, Lathia JD, Zhang P, Flavahan W, Rich JN and Mattson MP: Molecular targeting of TRF2 suppresses the growth and tumorigenesis of glioblastoma stem cells. Glia. 62:1687–1698. 2014. View Article : Google Scholar : PubMed/NCBI

157 

Simonet T, Zaragosi LE, Philippe C, Lebrigand K, Schouteden C, Augereau A, Bauwens S, Ye J, Santagostino M, Giulotto E, et al: The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats. Cell Res. 21:1028–1038. 2011. View Article : Google Scholar : PubMed/NCBI

158 

Cherfils-Vicini J, Iltis C, Cervera L, Pisano S, Croce O, Sadouni N, Győrffy B, Collet R, Renault VM, Rey-Millet M, et al: Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2. EMBO J. 38:e1000122019. View Article : Google Scholar : PubMed/NCBI

159 

Talmadge JE and Gabrilovich DI: History of myeloid-derived suppressor cells. Nat Rev Cancer. 13:739–752. 2013. View Article : Google Scholar : PubMed/NCBI

160 

Karlseder J, Broccoli D, Dai Y, Hardy S and de Lange T: p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 283:1321–1325. 1999. View Article : Google Scholar : PubMed/NCBI

161 

Pal D, Sharma U, Singh SK, Kakkar N and Prasad R: Over-expression of telomere binding factors (TRF1 & TRF2) in renal cell carcinoma and their inhibition by using SiRNA induce apoptosis, reduce cell proliferation and migration in vitro. PLoS One. 10:e01156512015. View Article : Google Scholar : PubMed/NCBI

162 

Bidzinska J, Baginski M and Skladanowski A: Novel anticancer strategy aimed at targeting shelterin complexes by the induction of structural changes in telomeric DNA: Hitting two birds with one stone. Curr Cancer Drug Targets. 14:201–216. 2014. View Article : Google Scholar : PubMed/NCBI

163 

Horikawa I, Fujita K and Harris CC: p53 governs telomere regulation feedback too, via TRF2. Aging (Albany NY). 3:26–32. 2011. View Article : Google Scholar : PubMed/NCBI

164 

Yang X, Li Z, Yang L, Lei H, Yu H, Liao Z, Zhou F, Xie C and Zhou Y: Knockdown of telomeric repeat binding factor 2 enhances tumor radiosensitivity regardless of telomerase status. J Cancer Res Clin Oncol. 141:1545–1552. 2015. View Article : Google Scholar : PubMed/NCBI

165 

Cabuy E, Newton C, Joksic G, Woodbine L, Koller B, Jeggo PA and Slijepcevic P: Accelerated telomere shortening and telomere abnormalities in radiosensitive cell lines. Radiat Res. 164:53–62. 2005. View Article : Google Scholar : PubMed/NCBI

166 

Zhong YH, Liao ZK, Zhou FX, Xie CH, Xiao CY, Pan DF, Luo ZG, Liu SQ and Zhou YF: Telomere length inversely correlates with radiosensitivity in human carcinoma cells with the same tissue background. Biochem Biophys Res Commun. 367:84–89. 2008. View Article : Google Scholar : PubMed/NCBI

167 

Orun O, Tiber PM and Serakinci N: Partial knockdown of TRF2 increase radiosensitivity of human mesenchymal stem cells. Int J Biol Macromol. 90:53–58. 2016. View Article : Google Scholar : PubMed/NCBI

168 

Ning HB, Li JC, Liu ZG and Fan DM: DNA damage increases telomerase activity and mRNA expression of telomeric repeat binding factor 2 in gastric cancer cells. Available in: www.cnki.net. World Chin J Digest. 14:942–946. 2006. View Article : Google Scholar

169 

Ning HB, Wang YH, Zhang LF, et al: Reversal of multidrug resistance in gastric cancer cells by telomeric repeat binding factor 2 small interfering RNA. Available in: www.cnki.net. Chin J Diges. 31:481–483. 2011.

170 

Benhamou Y, Picco V, Raybaud H, Sudaka A, Chamorey E, Brolih S, Monteverde M, Merlano M, Lo Nigro C, Ambrosetti D and Pagès G: Telomeric repeat-binding factor 2: A marker for survival and anti-EGFR efficacy in oral carcinoma. Oncotarget. 7:44236–44251. 2016. View Article : Google Scholar : PubMed/NCBI

171 

Roy S, Roy S, Kar M, Thakur S, Akhter Y, Kumar A, Delogu F, Padhi S, Saha A and Banerjee B: p38 MAPK pathway and its interaction with TRF2 in cisplatin induced chemotherapeutic response in head and neck cancer. Oncogenesis. 7:532018. View Article : Google Scholar : PubMed/NCBI

172 

Apetoh L, Végran F, Ladoire S and Ghiringhelli F: Restoration of antitumor immunity through selective inhibition of myeloid derived suppressor cells by anticancer therapies. Curr Mol Med. 11:365–372. 2011. View Article : Google Scholar : PubMed/NCBI

173 

Bruchard M, Mignot G, Derangère V, Chalmin F, Chevriaux A, Végran F, Boireau W, Simon B, Ryffel B, Connat JL, et al: Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med. 19:57–64. 2013. View Article : Google Scholar : PubMed/NCBI

174 

Sevko A, Michels T, Vrohlings M, Umansky L, Beckhove P, Kato M, Shurin GV, Shurin MR and Umansky V: Antitumor effect of paclitaxel is mediated by inhibition of myeloid-derived suppressor cells and chronic inflammation in the spontaneous melanoma model. J Immunol. 190:2464–2471. 2013. View Article : Google Scholar : PubMed/NCBI

175 

Wang M, Cao J, Zhu JY, Qiu J, Zhang Y, Shu B, Ou TM, Tan JH, Gu LQ, Huang ZS, et al: Curcusone C induces telomeric DNA-damage response in cancer cells through inhibition of telomeric repeat factor 2. Biochim Biophys Acta Proteins Proteom. 1865:1372–1382. 2017. View Article : Google Scholar : PubMed/NCBI

176 

Jiao Y, Zhang W, Liu J, Ni W, Xu W, Jin J and Qian W: Telomere attrition and chromosome instability via downregulation of TRF2 contributes to arsenic trioxide-induced apoptosis of human T-Cell leukemia cell line molt-4 cells. Cancer Biol Ther. 6:1186–1192. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang Z and Wu X: Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review). Oncol Rep 46: 184, 2021.
APA
Wang, Z., & Wu, X. (2021). Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review). Oncology Reports, 46, 184. https://doi.org/10.3892/or.2021.8135
MLA
Wang, Z., Wu, X."Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review)". Oncology Reports 46.2 (2021): 184.
Chicago
Wang, Z., Wu, X."Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review)". Oncology Reports 46, no. 2 (2021): 184. https://doi.org/10.3892/or.2021.8135
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Z and Wu X: Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review). Oncol Rep 46: 184, 2021.
APA
Wang, Z., & Wu, X. (2021). Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review). Oncology Reports, 46, 184. https://doi.org/10.3892/or.2021.8135
MLA
Wang, Z., Wu, X."Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review)". Oncology Reports 46.2 (2021): 184.
Chicago
Wang, Z., Wu, X."Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review)". Oncology Reports 46, no. 2 (2021): 184. https://doi.org/10.3892/or.2021.8135
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team