Grant: Travel Awards - Institute Community Support

Prostate cancer (PCa) affects one million men worldwide, and approximately 26% of these men die from PCa each year. Castration-resistant prostate cancer (CRPC) is the aggressive form of PCa that is resistant to most available therapies. The exact molecular mechanisms of how PCa develops into CRPC is unclear. Identifying such molecular mechanisms will allow the development of specific drugs targeting molecules involved in CRPC development and resistance. When comparing the translatome of androgen-dependent non-aggressive PCa tissues to CRPC tissues, we found that the expression levels of several nucleolar proteins are elevated in CRPC tissues. We found that the mRNA translation of D-E-A-D Box Helicase 55 (DDX55), a novel nucleolar protein, is elevated in CRPC tissues compared to non-aggressive tissues. The DEAD box proteins are a class of nucleolar proteins that contain highly conserved ATP-binding and RNA-binding sites. This protein family has been proven to play a key role in regulating RNA metabolism, which is crucial for cell growth and is involved in cancer progression. In non-cancer cells, the protein expression of DDX55 is relatively low, and the protein does not phase separate to form nucleolar compartments. However, in PCa and CRPC cells, the protein expression is significantly higher, and the protein translocates to the granular center of the nucleolus. Furthermore, we found that the gene expression of DDX55 is regulated by androgens; DDX55 expression is reduced in the tumors of castrated mice but elevated in CRPC mice. After this gene is silenced, we found that androgen receptor activities in CRPC cells are reduced by 80% compared to control CRPC cells. Moreover, silencing DDX55 only triggers CRPC cell death without disturbing normal prostate cell survival. Our results suggest that the altered expression of DDX55 plays a crucial role in prostate cancer progression, and it is a potential biomarker and therapeutic target for prostate cancer.