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). This evidence concerns the gene CLDN5 and Familial prostate cancer.