Targeting DNA Damage Response in Prostate Cancer by Inhibiting Androgen Receptor-CDC6-ATR-Chk1 Signaling

• Published in: Cell reports (Cambridge) Vol. 18; no. 8; pp. 1970 - 1981
• Main Authors: Karanika, Styliani, Karantanos, Theodoros, Li, Likun, Wang, Jianxiang, Park, Sanghee, Yang, Guang, Zuo, Xuemei, Song, Jian H., Maity, Sankar N., Manyam, Ganiraju C., Broom, Bradley, Aparicio, Ana M., Gallick, Gary E., Troncoso, Patricia, Corn, Paul G., Navone, Nora, Zhang, Wei, Li, Shuhua, Thompson, Timothy C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.02.2017; Elsevier
• Subjects: androgen receptor; Androgen Receptor Antagonists - pharmacology; Animals; Apoptosis - drug effects; Ataxia Telangiectasia Mutated Proteins - metabolism; ATR; AZD7762; Biomarkers - metabolism; CDC6; Cell Cycle Checkpoints - drug effects; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Checkpoint Kinase 1 - metabolism; Chk1; DNA damage; DNA Damage - drug effects; DNA Damage - physiology; DNA Replication - drug effects; DNA-Binding Proteins - metabolism; enzalutamide; Humans; Male; Mice; Mice, Nude; Nuclear Proteins - metabolism; Phosphorylation - drug effects; prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Receptors, Androgen - metabolism; Signal Transduction - drug effects; Thiophenes - pharmacology; TOPBP1; Urea - analogs & derivatives; Urea - pharmacology; prostate cancer; androgen receptor; DNA damage; AZD7762; CDC6; Chk1; TOPBP1; enzalutamide; ATR

Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7...