AKT1 and Familial prostate cancer: On the other hand, as claudin-5 is downregulated by vascular endothelial growth factor receptor-2 (VEGFR2)/PI3K/Akt signaling and IL-8 in endothelial cells, resulting in impaired endothelial integrity and increased vascular permeability (106), the reduction of claudin-5 may play a role in weakened cell adhesion and tumor metastasis in various tumor types, such as ovarian cancer (107), urothelial carcinoma (108), and prostate cancer (109).