Abstract 6727: Ecdysoneless (ECD) as a key estrogen-regulated protein driving progression in ER-positive breast cancer

Abstract Background: Breast cancer (BC) is a heterogenous disease, with estrogen receptor-positive (ER+) BC accounting for over 70% of cases. ER+ BC depend on estrogen signaling for oncogenesis and metastasis. Even though treatments targeting ER pathway have improved patient’s outcome, factors driving ER+ BC progression particularly in metastatic remain unclear. One of these factors is Ecdysoneless (ECD), a highly conserved protein from yeast to human. ECD expression correlates with ER expression, ECD overexpression is observed in ER+ BC and ECD overexpression correlates with poor patient survival. In this study, we assessed the relationship of ECD and ER, and the role of ECD in ER+ BC oncogenic traits. Methods: Bioinformatic analysis of publicly available datasets were explored for the relationship between ER and ECD and survival analysis was performed to examine the link between ECD, ER, and ER target MYC expression. ECD promoter analysis followed by chromatin immunoprecipitation (ChIP) and promoter-luciferase assays were used to assess estrogen-dependent ER recruitment to the ECD promoter. Estradiol (E2) treatments were performed to examine how estrogen signaling affects ECD levels. The effects of ECD overexpression were performed in ER+ breast cancer cells to evaluate changes in in vitro tumorigenic traits. Results: ECD expression correlated with ER levels in publicly available datasets. Survival data showed patients with elevated levels of ECD in ER+ BC had worse outcome. The ECD promoter contained estrogen response elements, and ChIP assays confirmed E2 mediated recruitment of ER to the ECD promoter. E2 treatment enhanced ECD promoter-luciferase activity. Overexpression of ECD in ER+ cells enhanced oncogenic traits. Conclusions: We have identified ECD is a novel estrogen regulated protein that plays a critical role in ER-driven oncogenesis in ER+ BC. Current studies are exploring the role of overexpressed ECD in in vivo preclinical mice models and therapy resistance. Citation Format: Farshid Oruji, Asher Rajkumar Rajan, Mohsin Raza, Bhopal Mohapatra, Hamid Band, Vimla Band. Ecdysoneless (ECD) as a key estrogen-regulated protein driving progression in ER-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6727.