Our results showed that CD147-high EVs activated the VEGF/AKT/eNOS/NO and AKT/mTOR/p70S6K signaling pathways, leading to endothelial cytoskeletal reorganization and internalization of VE-cadherin, which significantly compromised endothelial barrier integrity, increased vascular leakage, enhanced transendothelial migration of tumor cell, and promoted the formation of metastatic tumors. Here, AKT1 is linked to neoplasm.