Research Paper Volume 12, Issue 10 pp 9948—9958
Topoisomerase II-binding protein 1 promotes the progression of prostate cancer via ATR-CHK1 signaling pathway
- 1 Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- 2 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
- 3 Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22903, USA
- 4 Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Received: January 24, 2020 Accepted: April 18, 2020 Published: May 27, 2020https://doi.org/10.18632/aging.103260
How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
DDR: DNA damage respons; PCa: prostate cancer; TopBP1: Topoisomerase II-binding protein 1; TMA: tissue microarray; TCGA: The Cancer Genome Atlas; GS: Gleason Score; BCR-free survival: biochemistry recurrence-free survival; PSA: prostate-specific antigen; AR: Androgen receptor; ATRIP: ATR-interacting protein; qRT-PCR: quantitative reverse transcriptase-polymerase chain reaction; IHC: immunohistochemistry.