DNA damage response (DDR) plays an important role in the progression of cancers, including prostate cancer (PCa). Topoisomerase II-binding protein 1 (TopBP1) is an essential promotor of ATR-mediated DDR. Herein, we investigated the association between TopBP1 and PCa and determined its effect on the progression of PCa. The expression and clinical features of TopBP1 were analyzed using large-scale cohort of tissue microarray analyses and The Cancer Genome Atlas database, which indicated that TopBP1 was positively correlated with high Gleason Score, advanced clinical and pathological stages, the metastasis status. Multivariate analysis revealed that the upregulation of TopBP1 was an independent predictor for a worse biochemical recurrence-free survival (BCR-free survival). Furthermore, we discovered that downregulation of TopBP1 significantly suppressed the growth and migration ability of PCa lines by loss-of-function assays in vitro. Further mechanistic investigations clarified that TopBP1 promoted proliferation and migration by activating ATR-Chk1 signaling pathway.

中文翻译：

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拓扑异构酶II结合蛋白1通过ATR-CHK1信号通路促进前列腺癌的进展。

DNA损伤反应（DDR）在包括前列腺癌（PCa）在内的癌症进展中起着重要作用。拓扑异构酶II结合蛋白1（TopBP1）是ATR介导的DDR的重要启动子。在这里，我们调查了TopBP1和​​PCa之间的关联，并确定了其对PCa进程的影响。使用大规模组织微阵列分析和癌症基因组图谱数据库分析了TopBP1的表达和临床特征，表明TopBP1与格里森评分高，临床和病理分期，转移状态呈正相关。多变量分析显示，TopBP1的上调是导致较差的无生化复发生存期（无BCR生存期）的独立预测因素。此外，体外。进一步的机理研究表明，TopBP1通过激活ATR-Chk1信号通路促进了增殖和迁移。