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ATM 信号转导与癌症。

ATM signalling and cancer.

机构信息

Mammalian Genetics Lab, Cancer Research UK London Research Institute, London, UK.

出版信息

Oncogene. 2014 Jun 26;33(26):3351-60. doi: 10.1038/onc.2013.275. Epub 2013 Jul 15.

Abstract

ATM, the protein kinase mutated in the rare human disease ataxia telangiectasia (A-T), has been the focus of intense scrutiny over the past two decades. Initially this was because of the unusual radiosensitive phenotype of cells from A-T patients, and latterly because investigating ATM signalling has yielded valuable insights into the DNA damage response, redox signalling and cancer. With the recent explosion in genomic data, ATM alterations have been revealed both in the germline as a predisposing factor for cancer and as somatic changes in tumours themselves. Here we review these findings, as well as advances in the understanding of ATM signalling mechanisms in cancer and ATM inhibition as a strategy for cancer treatment.

摘要

ATM 是一种在罕见的人类疾病共济失调毛细血管扩张症(A-T)中发生突变的蛋白激酶,在过去的二十年中一直是人们关注的焦点。最初这是因为 A-T 患者的细胞具有异常的放射敏感性表型,而后来则是因为研究 ATM 信号转导为 DNA 损伤反应、氧化还原信号转导和癌症提供了有价值的见解。随着基因组数据的最近爆炸式增长,ATM 改变已经在种系中被揭示为癌症的易患因素,并且在肿瘤本身中也作为体细胞改变。在这里,我们回顾这些发现,以及对癌症中 ATM 信号转导机制的理解的进展,以及 ATM 抑制作为癌症治疗的一种策略。

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