Targeting Ezh2/Dab2ip/C-Jun Axis In Ovarian Cancer Stem Cells

Ovarian cancer (OC) is the leading cause of death from gynecologic malignancies. The persistence of quiescent OC stem cells (OCSCs) not eliminated by chemotherapy plays a key role in tumor relapse and metastasis. In the current study, we tested the hypothesis that targeting DAB2IP will inhibit OCSCs and prevent disease recurrence. Subpopulations of CSC and non-CSC were isolated from OC cell lines by fluorescence-activated cell sorting (FACS) based on aldehyde dehydrogenase (ALDH) activity, a consistent CSC marker. Expression of DAB2IP in ALDH(+) cells was lower (P 2) altered expression of 449 genes, including down-regulation of ALDH1A1, LGR5, PROM1 and TWIST1, markers strongly associated with CSC phenotypes. Ingenuity Pathway Analysis for upstream regulators of differentially expressed genes revealed WNT-signaling as a dominant pathway mediating the anti-OCSC effects of DAB2IP. Based on RNA-seq analysis, WNT5B expression decreased (P Citation Format: Xingyue Zong, Ali Ozes, Weini Wang, Fang Fang, Kenneth P. Nephew. Targeting EZH2/DAB2IP/C-JUN axis in ovarian cancer stem cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 498.