EVs released into TME either by tumor cells or stromal cells were shown to induce tumor angiogenesis, ECM remodeling and metastasis, albeit through activating known pro-angiogenic signaling molecules such as HIF, MMP, PI3K/AKT and LOX (King et al., 2012; Kucharzewska et al., 2013). This evidence concerns the gene AKT1 and neoplasm.