Topoisomerase II-binding protein 1 promotes the progression of prostate cancer via ATR-CHK1 signaling pathway
Open Access
- 31 May 2020
- journal article
- research article
- Published by Impact Journals, LLC in Aging
- Vol. 12 (10), 9948-9958
- https://doi.org/10.18632/aging.103260
Abstract
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.This publication has 32 references indexed in Scilit:
- Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiationCell Death & Disease, 2012
- International Variation in Prostate Cancer Incidence and Mortality RatesEuropean Urology, 2012
- Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapyCell Death & Differentiation, 2011
- Tethering DNA Damage Checkpoint Mediator Proteins Topoisomerase IIβ-binding Protein 1 (TopBP1) and Claspin to DNA Activates Ataxia-Telangiectasia Mutated and RAD3-related (ATR) Phosphorylation of Checkpoint Kinase 1 (Chk1)Online Journal of Public Health Informatics, 2011
- Regulation of p53 by TopBP1: a Potential Mechanism for p53 Inactivation in CancerMolecular and Cellular Biology, 2009
- Lead Time and Overdiagnosis in Prostate-Specific Antigen Screening: Importance of Methods and ContextJNCI Journal of the National Cancer Institute, 2009
- Living on a break: cellular senescence as a DNA-damage responseNature Reviews Cancer, 2008
- Characterization of the interaction between the human DNA topoisomerase IIβ-binding protein 1 (TopBP1) and the cell division cycle 45 (Cdc45) proteinBiochemical Journal, 2007
- Rad4TopBP1, a Scaffold Protein, Plays Separate Roles in DNA Damage and Replication Checkpoints and DNA ReplicationMolecular Biology of the Cell, 2006
- A DNA‐Topoisomerase‐11–Binding Protein with Eight Repeating Regions Similar to DNA‐repair Enzymes and to a Cell‐Cycle RegulatorJBIC Journal of Biological Inorganic Chemistry, 1997