Importantly, CX3CL1 was the central mediator in the interaction between circulating NSCLC cells and VBMECs: the master effector in the ICAM-1-dependant Src/GEF-H1 pathway to regulate VBMEC permeability, the main downstream effector in the NF-κB and MAPK14/ADMA17 pathways for NSCLC cells acting on VBMECs, and a pivotal player in the PI3K/AKT pathway enabling the VBMEC-induced increase of NSCLC cell invasive capacity. This evidence concerns the gene ARHGEF2 and non-small cell lung carcinoma.