Abstract B108: Zinc finger protein 217 (ZNF217) promotes ovarian cancer metastasis through interaction with estrogen

Abstract

Abstract ZNF217 is a transcription factor located at chromosomal region 20q13.2 which is frequently amplified in many human cancers, including ovarian. Consistently, ZNF217 mRNA is overexpressed in epithelial ovarian cancer and is negatively correlated with 5-year survival predictions. Despite this connection, little is known about the role of ZNF217 in the development of epithelial ovarian cancer. To explore the role of ZNF217 in this context, we generated ovarian cancer cell lines that stably overexpress ZNF217 to prolife in vitro pro-metastatic phenotypes. We found that increased expression of ZNF217 led to increases in cell proliferation, cell migration, adhesion, and transwell invasion. Subsequent gene expression analysis revealed alterations consistent with the induction of epithelial to mesenchymal transition (EMT). Depleting ZNF217 resulted in abrogation of these phenotypes. Consistent with these in vitro data, both intraperitoneal and ovary intrabursal xenograft models demonstrated that increased levels of ZNF217 rapidly enhanced the rate of tumorigenesis in vivo. RNA sequencing analyses revealed significant alterations in expression of genes involved in estrogen signaling, such as ESR1 and ESR2. We found that in vitro the presence of 17β-estradiol synergistically increased cell proliferation and invasion when compared to cells in media lacking estrogens. In vivo, ovariectomized mice supplemented with a subcutaneous slow release 17β-estradiol tablet in combination with high-ZNF217 expressing cells displayed an increased rate of tumorigenesis and an increase in disease severity as compared to controls lacking estrogens. The findings reveal a novel transcription factor that is key in promoting ovarian cancer progression and metastasis and highlights a functional role for estrogen in promoting ZNF217-driven metastasis. Citation Format: Kathryn Wardrup, Achuth Padmanabhan. Zinc finger protein 217 (ZNF217) promotes ovarian cancer metastasis through interaction with estrogen [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B108.