Discerning The Role Of Usp22 In Prostate Cancer Development And Progression

Prostate cancer (PCa) is the second leading cause of cancer-related death for men in the United States. While organ-confined disease is manageable, advanced and disseminated PCa currently has no durable treatment options. Thus, understanding the causes and consequences of the transition from early stage to late stage castrate-resistant PCa (CRPC) are critical. While this transition has a requisite for the androgen receptor (AR) activity, the mechanisms by which AR and other oncogenes are functionally increased, even after initial treatment with androgen deprivation therapy (ADT) have not been completely characterized. USP22, a known deubiquitinase associated with the SAGA transcriptional activation complex, was originally designated in a “death from cancer” gene signature. Importantly, USP22 is significantly upregulated in PCa patients with late-stage disease, and specifically indicates for poor outcome in PCa patients. Moreover, tumor-associated USP22 increases AR levels and activity as well as the oncogene MYC function, partially defining the mechanism by which tumor-associated USP22 drives PCa progression. Thus, while certain consequences of tumor-associated USP22 expression have been elucidated, the remaining downstream effects have not been thoroughly characterized. Newly generated data begin to establish the biochemical events controlled by USP22 that confer proliferation and survival on PCa cells. Through use of novel proteomic technology, specifically Ubiscan analysis, tumor-associated USP22 will be shown to participate in driving PCa development and progression as well as therapeutic bypass through differential regulation of the ubiquitylome. Citation Format: Jennifer Jones, Jeffry L. Dean, Randy S. Schrecengost, Karen Knudsen. Discerning the role of USP22 in prostate cancer development and progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1862. doi:10.1158/1538-7445.AM2015-1862