Abstract B157: Understanding the role of transcription factor ETV1 in metabolic reprogramming of prostate cells as a route to novel therapeutics.

ETV1 is the second most frequently rearranged ETS transcription factor gene in human prostate cancer. It is widely believed that ectopically expressed ETV1 (due to gene fusions) plays a similar role in prostate tumorigenesis to that of ERG. However, further analysis of clinical data revealed that high levels of ETV1 expression are often found in more advanced prostate cancers, whereas ERG overexpression is mainly associated with localized prostate cancer and elevated androgen receptor signaling. High expression of ETV1, rather than ERG, in the prostate has been associated with disease recurrence in some patients. Interestingly, many metabolic pathways often associated with cancer cells are enriched in the prostates of mice engineered to carry a Tmprss2-ETV1 knockin allele and ETV1-expressing human prostate cancer samples. To determine the dominant metabolic programs that accompany ETV1 expression, we have performed metabolic profiling, and integrated the data with human prostate cells and mouse transcriptome data. Our analyses have identified ETV1 as a regulator of lipid metabolism, glycolysis and glutamine metabolism. Of note, ETV1 expression reprograms the steroid biosynthesis pathway, leading to an increase in testosterone production at least in part through 17-β hydroxysteorid dehydrogenases activation. Indeed, one of the main causes of prostate cancer recurrence is local androgen production due to metabolic changes in prostate cancer cells. This novel finding may explain, at least in part, how ETV1 expression promotes castration-resistant disease, opening a new path to the development of novel therapies directed to progressive and lethal prostate cancer.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B157.

Citation Format: Esther Baena, Shahan Mamoor, Zhe Li, Stuart H. Orkin. Understanding the role of transcription factor ETV1 in metabolic reprogramming of prostate cells as a route to novel therapeutics. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B157.