Identification of Novel Targetable NPC-Mitotic Regulated Mechanisms in Lethal Prostate Cancer

Nuclear Pores are protein complexes embedded within the nuclear envelope (NE) of cells that regulate a wide range of critical cellular functions including genome integrity, gene expression and cell division. Alterations in the NE, the Nuclear Pore Complex (NPC), and in nucleoporins, which are the components of NPCs, are often observed in cancer cells. However, the specific nucleoporins and nucleoporin-based mechanisms contributing to cancer remain ill-defined, while their role in prostate cancer is completely unknown. Veronica Rodriguez-Bravo is studying the role of nucleoporins and NPCs in prostate cancer progression. Rodriguez-Bravo has observed NPC alterations in prostate cancer and identified POM121 as being the most upregulated nucleoporin in aggressive prostate cancer. The effects of POM121 upregulation on genome stability and cell division rates will be investigated in prostate cancer cell lines. Pathways involved in genomic stability and cell division that are affected by changes in POM121 will be identified. Whether POM121-based effects are associated with responses to conventional and experimental prostate cancer treatments will be investigated in preclinical prostate cancer models. If successful, this project will identify the contribution of nuclear pores to prostate cancer aggressiveness, identify novel targetable pathways, and determine whether NPCs may act as biomarkers to improve the clinical management of prostate cancer patients.