Results revealed that tumor or host-derived PGE2 in the tumor micro-environment or exogenous PGE2 or EP4 agonists can directly stimulate lymphangiogenesis by activation of EP4 receptors on the LEC via PI3K/Akt and Erk signaling pathways and VEGFR-3 stimulation, so that EP4 antagonists may be useful in the prevention and intervention of lymphatic metastasis in breast cancer. This evidence concerns the gene AKT1 and neoplasm.