Abstract 1113: Inhibition of DNA repair by NR1D1 enhances chemosensitivity of breast cancer cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-07, Vol.77 (13_Supplement), p.1113-1113
• Main Authors: Ka, Na-Lee, Lee, Mi-Ock
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-1113

Most chemotherapeutic agents exert cytotoxic effects by inducing excessive DNA lesions in cancer cells. Therefore, regulating DNA repair networks is a critical factor that determines sensitivity of cancer cells to chemotherapeutic drugs. In this study, we identified the role of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited recruitment of the DNA repair complex to damaged DNA sites, thereby impaired proper DNA repair upon doxorubicin treatment in breast cancer cells. Interaction with Poly(ADP-ribose) polymerase-1 and subsequent PARylation were critical steps that allow NR1D1 to translocate to DNA double-strand breaks. In agreement, depletion of NR1D1 in MCF-7 cells resulted in resistance to a chemotherapeutic drug, doxorubicin, in both in vitro and in vivo experiments. Further, NR1D1 expression level was correlated positively with clinical outcomes in breast cancer patients who received chemotherapy. Thus, NR1D1 and its ligands may provide better therapeutic options that could enhance the outcomes of adjuvant chemotherapy in breast cancer patients. Citation Format: Na-Lee Ka, Tae-Young Na, Hyelin Na, Mi-Ock Lee. Inhibition of DNA repair by NR1D1 enhances chemosensitivity of breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1113. doi:10.1158/1538-7445.AM2017-1113