Mechanism and Function of Angiogenin in Prostate Cancer.

Angiogenin (ANG), the fifth member of the vertebrate-specific ribonuclease (RNase) A superfamily, is a secreted angiogenic ribonuclease strongly up-regulated in human prostate cancers. ANG is translocated to the nucleus in both prostate cancer epithelial cells and endothelial cells to exert its role in prostate cancer progression by mediating tumor angiogenesis, cancer cell survival and proliferation through rRNA biogenesis. ANG-stimulated rRNA is required not only for prostate intraepithelial neoplasia (PIN) formation, but also for androgen-independent growth of prostate cancer cells. Targeting ANG by various antagonists that inhibit its nuclear translocation, function and/or activity has proven to inhibit prostate cancer growth in animal models. Furthermore, the role of ANG in androgen independence has been firmly established, suggesting a strong rationale for therapeutically targeting ANG in the treatment of castration resistant prostate cancer.