Mechanism underlying CDC20 affecting epithelial ovarian cancer biological behavior by regulating BAG6 ubiquitination

Xiaocui Zhang; Fangfang Bi; Qing Yang

doi:10.1016/j.cellsig.2024.111577

Mechanism underlying CDC20 affecting epithelial ovarian cancer biological behavior by regulating BAG6 ubiquitination

Cell Signal. 2024 Dec 20:127:111577. doi: 10.1016/j.cellsig.2024.111577. Online ahead of print.

Authors

Xiaocui Zhang¹, Fangfang Bi¹, Qing Yang²

Affiliations

¹ Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.
² Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China. Electronic address: yangqing_sj@126.com.

PMID: 39710091
DOI: 10.1016/j.cellsig.2024.111577

Abstract

Epithelial ovarian cancer (EOC) endangers women's life and health. It is reported that cell division cycle 20 (CDC20) plays a role in EOC, but its underlying mechanisms remain unclear. Additionally, the involvement of bcl-2-associated athanogen-6 (BAG6) in EOC has not been previously reported. This study demonstrated that CDC20 was highly expressed in EOC and exhibited oncogenic properties through both in vitro and in vivo molecular biology experiments. In contrast, BAG6 was low expressed and functioned as a tumor suppressor. Both CDC20 and BAG6 were found to correlate with patient stage. Notably, the degradation of BAG6, mediated by CDC20 via ubiquitin-proteasome pathway, was shown to enhance the malignant biological behavior of EOC. Furthermore, the interaction between CDC20 and BAG6 was dependent on the WD40 domain of CDC20 and the D-box of BAG6. These findings provided valuable insights into the molecular mechanisms of EOC and established a theoretical basis for novel therapeutic targets in clinical treatment.

Keywords: BAG6; CDC20; Epithelial ovarian cancer; Ubiquitination.