ECD, a novel androgen receptor target promotes prostate cancer tumorigenesis by regulating glycolysis

Raza, M.; Rajan, A. R.; Kennedy, B. B.; Reznicek, T. E.; Oruji, F.; Mirza, S.; Rowley, M. J.; Kristiansen, G.; Datta, K.; Mohapatra, B. C.; Band, H.; Band, V.

doi:10.1101/2025.01.30.635534

bioRxiv · 10.1101/2025.01.30.635534

ECD, a novel androgen receptor target promotes prostate cancer tumorigenesis by regulating glycolysis

Raza, M.·Rajan, A. R.·Kennedy, B. B.·Reznicek, T. E.·Oruji, F.·Mirza, S.·Rowley, M. J.·Kristiansen, G.·Datta, K.·Mohapatra, B. C.·Band, H.·Band, V.

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Abstract

Androgen receptor (AR)-mediated signaling is essential for PC tumorigenesis. In the TCGA database we observed a positive correlation between ECD and AR expression. Consistently, Dihydrotestosterone (DHT) treatment of PC cell lines increased ECD mRNA and protein levels, and AR knockdown (KD) reduced ECD expression. Bioinformatic analysis predicted three consensus androgen response elements in the ECD promoter, and DHT treatment increased AR occupancy at the ECD promoter, and enhanced ECD promoter activity. Enzalutamide treatment decreased ECD levels, and ECD knockout (KO) in PC cells reduced oncogenic traits, suggesting a functional role of ECD to maintain PC oncogenesis. ECD mRNA and protein are overexpressed in PC patient tissues, and its overexpression predicts shorter survival. Overexpression of ECD in PC cell lines enhanced the oncogenic traits in vitro and developed faster and larger highly proliferative xenograft tumors. RNA-seq analysis of mouse tumors revealed an increase in mRNA levels of several glycolytic genes. ECD associates with mRNA of key glycolytic genes and is required for their stability, consistent with our recent demonstration of ECD is an RNA binding protein. Higher glucose uptake and glycolysis was seen upon ECD overexpression in PC cells. Together, we demonstrate the role of a novel AR target gene ECD in PC tumorigenesis.

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Raza, M., Rajan, A. R., Kennedy, B. B., Reznicek, T. E., Oruji, F., Mirza, S., Rowley, M. J., Kristiansen, G., Datta, K., Mohapatra, B. C., Band, H., Band, V.. 2025-02-05. ECD, a novel androgen receptor target promotes prostate cancer tumorigenesis by regulating glycolysis. https://doi.org/10.1101/2025.01.30.635534

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