Role of Telomeres and Telomerase in Aging and Cancer

被引:468
作者
Shay, Jerry W. [1 ,2 ]
机构
[1] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, 5323 Harry Hines Blvd, Dallas, TX 75930 USA
[2] King Abdulaziz Univ, Ctr Excellence Genom Med Res, Jeddah 21413, Saudi Arabia
关键词
TERT PROMOTER MUTATIONS; CELLULAR SENESCENCE; INHIBITOR IMETELSTAT; CATALYTIC SUBUNIT; LIFE-SPAN; IMMORTAL CELLS; DNA-DAMAGE; LENGTH; MECHANISMS; RISK;
D O I
10.1158/2159-8290.CD-16-0062
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Telomeres progressively shorten throughout life. A hallmark of advanced malignancies is the ability for continuous cell divisions that almost universally correlates with the stabilization of telomere length by the reactivation of telomerase. The repression of telomerase and shorter telomeres in humans may have evolved, in part, as an anticancer protection mechanism. Although there is still much we do not understand about the regulation of telomerase, it remains a very attractive and novel target for cancer therapeutics. This review focuses on the current state of advances in the telomerase area, identifies outstanding questions, and addresses areas and methods that need refinement. Significance: Despite many recent advances, telomerase remains a challenging target for cancer therapy. There are few telomerase-directed therapies, and many of the assays used to measure telomeres and telomerase have serious limitations. This review provides an overview of the current state of the field and how recent advances could affect future research and treatment approaches. (C) 2016 AACR.
引用
收藏
页码:584 / 593
页数:10
相关论文
共 102 条
  • [21] TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY
    COUNTER, CM
    AVILION, AA
    LEFEUVRE, CE
    STEWART, NG
    GREIDER, CW
    HARLEY, CB
    BACCHETTI, S
    [J]. EMBO JOURNAL, 1992, 11 (05) : 1921 - 1929
  • [22] Shelterin: the protein complex that shapes and safeguards human telomeres
    de Lange, T
    [J]. GENES & DEVELOPMENT, 2005, 19 (18) : 2100 - 2110
  • [23] STRUCTURE AND VARIABILITY OF HUMAN-CHROMOSOME ENDS
    DELANGE, T
    SHIUE, L
    MYERS, RM
    COX, DR
    NAYLOR, SL
    KILLERY, AM
    VARMUS, HE
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1990, 10 (02) : 518 - 527
  • [24] Estimating telomere length from whole genome sequence data
    Ding, Zhihao
    Mangino, Massimo
    Aviv, Abraham
    Spector, Tim
    Durbin, Richard
    [J]. NUCLEIC ACIDS RESEARCH, 2014, 42 (09) : e75
  • [25] Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation
    Fumagalli, Marzia
    Rosiello, Francesca
    Clerici, Michela
    Barozzi, Sara
    Cittaro, Davide
    Kaplunov, Jessica M.
    Bucci, Gabriele
    Dobreva, Miryana
    Matti, Valentina
    Beausejour, Christian M.
    Herbig, Utz
    Longhese, Maria Pia
    di Fagagna, Fabrizio d'Adda
    [J]. NATURE CELL BIOLOGY, 2012, 14 (04) : 355 - +
  • [26] Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination
    Gomes, Nuno M. V.
    Ryder, Oliver A.
    Houck, Marlys L.
    Charter, Suellen J.
    Walker, William
    Forsyth, Nicholas R.
    Austad, Steven N.
    Venditti, Chris
    Pagel, Mark
    Shay, Jerry W.
    Wright, Woodring E.
    [J]. AGING CELL, 2011, 10 (05) : 761 - 768
  • [27] Comparative genetics of longevity and cancer: insights from long-lived rodents
    Gorbunova, Vera
    Seluanov, Andrei
    Zhang, Zhengdong
    Gladyshev, Vadim N.
    Vijg, Jan
    [J]. NATURE REVIEWS GENETICS, 2014, 15 (08) : 531 - 540
  • [28] Greaves M, 2015, NUCLEIC ACIDS RES, V314, P1806
  • [29] IDENTIFICATION OF A SPECIFIC TELOMERE TERMINAL TRANSFERASE-ACTIVITY IN TETRAHYMENA EXTRACTS
    GREIDER, CW
    BLACKBURN, EH
    [J]. CELL, 1985, 43 (02) : 405 - 413
  • [30] Mammalian telomeres end in a large duplex loop
    Griffith, JD
    Comeau, L
    Rosenfield, S
    Stansel, RM
    Bianchi, A
    Moss, H
    de Lange, T
    [J]. CELL, 1999, 97 (04) : 503 - 514