Abstract 266: Androgen regulated ECD overexpression promotes prostate cancer tumorigenesis through increased glycolysis

Abstract Introduction: Prostate cancer (PC) is the most diagnosed cancer in males. Androgen receptor (AR) signaling is essential for PC progression. ECD (Ecdysoneless) protein participates in cell cycle progression and cell survival and is overexpressed in non-PC cancers. Current study explored the role and function of ECD in PC progression. Methods: TCGA Prostate Adenocarcinoma database was used to assess correlation between ECD and AR expression, and ECD’s expression in PC dataset. Bioinformatic analysis was performed to predict androgen response elements in the ECD promoter. Chromatin immunoprecipitation (ChIP) and Promoter-Luciferase assays were used to assess AR recruitment to the ECD promoter. ECD was overexpressed, as well as crispr knocked out in hormone-dependent LNCaP and hormone-independent C4-2B PC cell lines. RNA-seq analysis was performed to assess transcriptomics changes in ECD-overexpressing (ECD-OE) tumors. RNA immunoprecipitation (RIP) was performed to assess ECD protein association to RNAs. Glucose uptake, and glycolytic rates assays were carried out to assess glycolysis. Results: ECD is overexpressed in PC patients’ tissues as compared to hyperplasia prostate samples, and ECD overexpression is associated with short patient survival. A significant positive correlation was observed between ECD and AR expression. Consensus androgen response elements in the ECD promoter showed androgen dependent recruitment of AR to the ECD promoter by ChIP assay. Luciferase assays showed androgen-dependent increase in ECD-luciferase activity. ECD overexpression and knockout in both LNCaP and C4-2B PC cell lines showed enhanced and decreased oncogenic traits, respectively. In vivo mice xenograft experiments showed ECD overexpression in LNCaP led to a significant increase in tumorigenesis. RNA-seq showed ECD overexpression led to increased levels of key glycolytic genes, which was confirmed by qRT-PCR. RIP assay revealed that ECD associates with the mRNA of these key glycolytic genes and enhances their stability. Functionally, ECD overexpressing PC cells showed higher glucose uptake and glycolytic rates, as compared to vector cells. Conclusion: Overall, our results demonstrate a novel role for androgen-regulated ECD overexpression in PC tumorigenesis through direct binding and stabilization of mRNAs of key glycolytic genes. Citation Format: Mohsin Raza, Asher Rajkumar Rajan, Benjamin B. Kennedy, Timothy E. Reznicek, Farshid Oruji, Sameer Mirza, M Jordan Rowley, Glen Kristiansen, Bhopal C. Mohapatra, Hamid Band, Vimla Band. Androgen regulated ECD overexpression promotes prostate cancer tumorigenesis through increased glycolysis [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 266.