Abstract 2526: Modulation of metastatic factors in prostate cancer cells by DAX-1 (NR0B1), an androgen-induced orphan nuclear receptor

Abstract

Abstract DAX-1, a member of the nuclear hormone receptor superfamily, has a pivotal role in adrenal and gonadal development. However, recent studies have shown that DAX-1 acts as a transcriptional repressor influencing the progression of many types of cancers. We hypothesize that DAX-1 has key roles in regulating metastatic genes during prostate cancer progression. We found that introducing DAX-1 into prostate cancer cells lacking endogenous expression of DAX-1 leads to a decrease in metastatic rates. Consequently, we analyzed DAX-1 transcriptional regulation over different markers associated with metastasis. Since the androgen receptor is a key regulator of prostate cancer progression, we used CRISPR to knockout DAX-1 expression in hormone-dependent prostate cancer cells, allowing us to understand the role DAX-1 has as a negative regulator of metastatic genes after androgen receptor activation. We have shown that treatment of hormone-dependent prostate cancer cells with a non-aromatizable androgen leads to upregulation of DAX-1 expression. Here we use the same mechanism to induce DAX-1 expression and analyze the effects on metastatic markers. Results have shown that DAX-1 is sufficient to decrease the expression of metastatic markers and inhibit metastatic rates in prostate cancer cells. These results further explain some of the intrinsic mechanisms involved in prostate cancer metastasis and could reveal new therapeutic routes in the treatment of metastatic prostate cancer. Citation Format: Roxxana Valeria Beltran Valencia, Christina Tzagarakis-Foster. Modulation of metastatic factors in prostate cancer cells by DAX-1 (NR0B1), an androgen-induced orphan nuclear receptor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2526.