Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer
Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer
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DOI：
10.1038/onc.2008.483
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发表时间：
2009-03-01
期刊：
影响因子：
8
通讯作者：
Ashworth, A.
中科院分区：
文献类型：
--
作者：
McCabe, N.;Cerone, M. A.;Ashworth, A.
BRCA1和BRCA2蛋白参与维持基因组稳定性，BRCA1或BRCA2中的生殖系功能丧失突变强烈地使携带者易患乳腺癌和其他器官癌。以前已经证明，细胞DNA维持途径的抑制元件代表了治疗这些个体中肿瘤的新治疗方法。在这里，我们表明，抑制端粒相关蛋白，端锚聚合酶1，也是选择性致命的BRCA缺乏症。我们还证明了抑制端锚聚合酶1引起的选择性与BRCA缺乏相关的中心体扩增表型的恶化有关。我们认为，Tankyrase 1的抑制可以用于BRCA相关癌症的治疗。
The BRCA1 and BRCA2 proteins are involved in the maintenance of genome stability and germ-line loss-of-function mutations in either BRCA1 or BRCA2 strongly predispose carriers to cancers of the breast and other organs. It has been demonstrated previously that inhibiting elements of the cellular DNA maintenance pathways represents a novel therapeutic approach to treating tumors in these individuals. Here, we show that inhibition of the telomere-associated protein, Tankyrase 1, is also selectively lethal with BRCA deficiency. We also demonstrate that the selectivity caused by inhibition of Tankyrase 1 is associated with an exacerbation of the centrosome amplification phenotype associated with BRCA deficiency. We propose that inhibition of Tankyrase 1 could be therapeutically exploited in BRCA-associated cancers.