Role of telomeres and telomerase in cancer.
Role of telomeres and telomerase in cancer.
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DOI：
10.1016/j.semcancer.2011.10.001
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发表时间：
2011-12
影响因子：
14.5
通讯作者：
Wright WE
中科院分区：
文献类型：
--
作者：
Shay JW;Wright WE
越来越多的证据表明端粒和端粒酶与细胞衰老和癌症之间存在重要关系。正常的人类细胞随着每次细胞分裂逐渐失去端粒，直到一些短的端粒变得无帽，导致称为复制性衰老的生长停滞。在没有基因组改变的情况下，这些细胞不会死亡，而是保持静止，与年轻的静止细胞相比，产生不同的蛋白质群。在特定的遗传和表观遗传改变后，正常的人类细胞绕过复制衰老并继续增殖，直到许多端粒末端变得无帽，导致称为危机的现象。在危机中，细胞具有严重缩短的端粒，但继续尝试分裂，导致显著的细胞死亡（凋亡）和进行性基因组不稳定。人类细胞很少能逃脱危机，这些细胞几乎普遍表达核糖核蛋白、端粒酶，并保持稳定但较短的端粒。端粒酶的激活可以被认为是一种机制，以减缓由于端粒功能失调而导致的基因组不稳定性。虽然端粒酶并不驱动致癌过程，但它是最晚期癌症持续生长所必需的。由于端粒酶在大多数正常人类细胞中不表达，这导致了目前处于高级临床试验中的靶向端粒酶癌症治疗方法的发展。
There is mounting evidence for the existence of an important relationship between telomeres and telomerase and cellular aging and cancer. Normal human cells progressively lose telomeres with each cell division until a few short telomeres become uncapped leading to a growth arrest known as replicative aging. In the absence of genomic alterations these cells do not die but remain quiescent producing a different constellation of proteins compared to young quiescent cells. Upon specific genetic and epigenetic alterations, normal human cells bypass replicative senescence and continue to proliferate until many telomere ends become uncapped leading to a phenomenon known as crisis. In crisis cells have critically shortened telomeres but continue to attempt to divide leading to significant cell death (apoptosis) and progressive genomic instability. Rarely, a human cell escapes crisis and these cells almost universally express the ribonucleoprotein, telomerase, and maintain stable but short telomeres. The activation of telomerase may be thought of as a mechanism to slow down the rate genomic instability due to dysfunctional telomeres. While telomerase does not drive the oncogenic process, it is permissive and required for the sustain growth of most advanced cancers. Since telomerase is not expressed in most normal human cells, this has led to the development of targeted telomerase cancer therapeutic approaches that are presently in advanced clinical trials.
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DOI：
10.1016/0921-8734(91)90018-7
发表时间：
1991-03-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
HARLEY, CB
通讯作者：
HARLEY, CB
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
3.3
作者：
Langford, LA;Piatyszek, MA;Shay, JW
通讯作者：
Shay, JW
影响因子：
8.4
作者：
Shay, JW;Bacchetti, S
通讯作者：
Bacchetti, S
影响因子：
5.3
作者：
WRIGHT, WE;PEREIRASMITH, OM;SHAY, JW
通讯作者：
SHAY, JW