Nucleotide metabolism, oncogene-induced senescence and cancer.

Nucleotide metabolism, oncogene-induced senescence and cancer.
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DOI:
10.1016/j.canlet.2014.01.017
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发表时间:
2015-01-28
期刊:
影响因子:
9.7
通讯作者:
Zhang, Rugang
Zhang, Rugang
中科院分区:
医学1区
文献类型:
--
作者:
Aird, Katherine M.;Zhang, Rugang

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衰老被定义为稳定的细胞生长停滞。癌基因诱导的衰老(OIS)发生在一个激活的癌基因在正常细胞中表达。OIS作为一种真正的肿瘤抑制机制,通过驱动携带初始致癌命中的癌症祖细胞的稳定生长停滞来发挥作用。OIS通常以异常DNA复制和相关的DNA损伤反应为特征。核苷酸,特别是脱氧核糖核苷酸三磷酸(dNTP),是DNA复制和修复所必需的。不平衡的dNTP池在许多人类疾病中发挥作用,包括在癌症发展的早期阶段。本文将重点介绍目前已知的核苷酸代谢减少在OIS中的作用,核苷酸代谢如何导致转化和肿瘤进展,以及如何通过诱导癌细胞衰老将此途径作为癌症治疗的靶点。
Senescence is defined as a stable cell growth arrest. Oncogene-induced senescence (OIS) occurs when an activated oncogene is expressed in a normal cell. OIS acts as a bona fide tumor suppressor mechanism by driving stable growth arrest of cancer progenitor cells harboring the initial oncogenic hit. OIS is often characterized by aberrant DNA replication and the associated DNA damage response. Nucleotides, in particular deoxyribonucleotide triphosphates (dNTPs), are necessary for both DNA replication and repair. Imbalanced dNTP pools play a role in a number of human diseases, including during the early stages of cancer development. This review will highlight what is currently known about the role of decreased nucleotide metabolism in OIS, how nucleotide metabolism leads to transformation and tumor progression, and how this pathway can be targeted as a cancer therapeutic by inducing senescence of cancer cells.
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