A Novel Mechanism to Induce BRCAness in Cancer Cells.
A Novel Mechanism to Induce BRCAness in Cancer Cells.
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DOI：
10.1158/0008-5472.can-20-1451
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发表时间：
2020-07-15
期刊：
影响因子：
11.2
通讯作者：
Cai C
中科院分区：
文献类型：
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作者：
Cai C
具有BRCA1或BRCA2种系有害突变的癌细胞缺乏同源重组修复，因此对PARP抑制剂治疗敏感。然而，在其他DNA损伤修复途径组分中存在缺陷的表达brca1 /2的野生型细胞也可能表现出“BRCAness”，这与PARP抑制相结合，同样可以诱导合成致死。在这一期的《癌症研究》杂志上，Luo及其同事报道了一种新的机制，即DNA双链断裂时BRCA1蛋白降解是由脯氨酸异构酶Pin 1调节的。Pin1的失活可以在癌细胞中建立BRCAness，从而使细胞对PARP抑制剂治疗敏感。
Cancer cells with germline deleterious mutations of BRCA1 or BRCA2 are deficient in homologous recombination repair and therefore sensitive to PARP inhibitor treatment. However, wild-type BRCA1/2-expressing cells with defects in other DNA damage repair pathway components may also exhibit “BRCAness”, which in combination with PARP inhibition can similarly induce synthetic lethality. In this issue of Cancer Research, Luo and colleagues report a novel mechanism by which BRCA1 protein degradation in response to DNA double-strand breaks is regulated by prolyl isomerase Pin 1. Inactivation of Pin1 can establish BRCAness in cancer cells and thus sensitize cells to PARP inhibitor treatment.