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端粒生物学在癌症中的作用。

The role of telomere biology in cancer.

机构信息

Department of Microbiology, University of California-Davis, CA 95616, USA.

出版信息

Annu Rev Pathol. 2013 Jan 24;8:49-78. doi: 10.1146/annurev-pathol-020712-164030. Epub 2012 Aug 28.

Abstract

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Although telomere dysfunction resulting from replicative attrition constrains tumor growth by engaging DNA-damage signaling pathways, it can also promote tumorigenesis by causing oncogenic chromosomal rearrangements. Expression of the telomerase enzyme enables telomere-length homeostasis and allows tumor cells to escape the antiproliferative barrier posed by short telomeres. Telomeres and telomerase also function independently of one another. Recent work has suggested that telomerase promotes cell growth through pathways unrelated to telomere maintenance, and a subset of tumors elongate telomeres through telomerase-independent mechanisms. In an effort to exploit the integral link between telomere biology and cancer growth, investigators have developed several telomerase-based therapeutic strategies, which are currently in clinical trials. Here, we broadly review the state of the field with a particular focus on recent developments of interest.

摘要

端粒生物学在癌症的发生和发展中起着关键而复杂的作用。尽管由于复制损耗导致的端粒功能障碍通过 DNA 损伤信号通路限制了肿瘤生长,但它也可以通过引起致癌染色体重排来促进肿瘤发生。端粒酶的表达使端粒长度保持稳定,并使肿瘤细胞能够逃避由短端粒引起的抗增殖障碍。端粒和端粒酶也可以相互独立地发挥作用。最近的研究表明,端粒酶通过与端粒维持无关的途径促进细胞生长,并且一部分肿瘤通过非端粒酶依赖的机制延长端粒。为了利用端粒生物学和癌症生长之间的内在联系,研究人员已经开发了几种基于端粒酶的治疗策略,这些策略目前正在临床试验中。在这里,我们广泛地回顾了这一领域的现状,特别关注了最近的一些相关进展。

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