We report that the PCAIs (1) suppress 2D and 3D NSCLC migration and invasion; (2) induce morphological changes promoting cell rounding; (3) disrupt F-actin organization and diminish filopodia density and (4) diminish Rac1, Cdc42 and RhoA protein levels but do not alter RhoA localization to compromise their functions in cytoskeletal organization. Here, CDC42 is linked to non-small cell lung carcinoma.