In summary, our study demonstrates that rVP1 downregulates integrin/FAK/PI3K and PIP3 as well as ILK and phospho-Akt in the raft domains to attenuate IKK/NF-κB signaling and reduce COX-2 and MIG-7 level leading to suppression of EMT and the invasion/metastasis of lung cancer cells in vitro and in vivo. Here, PTK2 is linked to lung carcinoma.