The role of Cripto signaling in lethal prostate cancer

Prostate cancer (PCa) is the most frequently diagnosed malignancy and second leading cause of cancer specific deaths in men worldwide. Although PCa can be effectively treated in its early stages with surgery and androgen deprivation therapy, the cancer becomes castration resistant and refractory to available therapies in a significant fraction of patients. In fact, PCa is heterogenous and contains small, possibly distinct subpopulations of cells with stem-like properties that have self-renewal and tumor/metastasis initiating capacity. Castration resistance PCa (CRPC) is thought to arise from this pre-existing subpopulation that survive androgen-deprivation therapy (castration) in a dormant state and then re-initiate tumor growth and metastasis. Therefore, it is critical to identify and target signaling pathways that fuel these cells and drive the castration resistant stage of the disease associated with metastasis and poor patient survival. We aim to investigate the role of the fetal oncoprotein Cripto in primary and castration resistant PCa. Cripto is a glycosyl-phosphatidylinositol (GPI) anchored protein that regulates stem cell- associated signaling pathways and promotes cellular plasticity, epithelia to mesenchymal transition and maintenance of the stem cell state during normal development, tissue homeostasis and tumorigenesis.

Elisa Rodrigues Sousa