Grant: Travel Awards - Institute Community Support

Prostate cancer (PCa) is a leading cause of cancer-related death in men, and castration-resistant prostate cancer (CRPC) represents an aggressive form of PCa that is resistant to standard therapies. It is critical to understand the molecular mechanisms driving CRPC for the development of new therapies. A key feature of PCa is the enlargement of the nucleolus, a part of the cell crucial for protein synthesis; this enlargement helps cells grow and multiply more quickly, promoting PCa. We have identified a new nucleolar protein Lysine-rich Nucleolar Protein 1 (KNOP1) whose expression is indicative of PCa aggressiveness. Interestingly, silencing KNOP1 in CRPC cells results in the condensation of the enlarged nucleoli and reduced cancer growth, suggesting that KNOP1 might be critical for nucleolar morphology and CRPC development. To further study KNOP1's role, we screened for its interactors and identified the TRiC/CCT complex. TRiC/CCT plays an essential role in protein folding and works alongside transporters that help localize the new proteins to their respective cell compartments. Though studies have linked TRiC/CCT to several cancers, their role in PCa remains unexplored. We hypothesize that KNOP1 works alongside TRiC/CCT to enhance protein folding and delivery to the nucleolus, supporting CRPC progression. Our goal is to uncover the KNOP1-TRiC/CCT mediated pathways unique to CRPC through studying their fundamental functions, delineating how these roles are exploited in PCa, and understanding the correlation between their expression and the progression of CRPC. We believe that identifying these molecular features unique to CRPC will contribute to the development of novel therapeutic targets that will successfully eliminate CRPC.