(1) NEDD4 mediates the EGF-stimulated lung cancer cell migration; (2) NEDD4 does not ubiquitinate and down-regulate of PTEN and activate the PI3K/AKT pathway; (3) NEDD4 facilitates the EGFR-dependent lysosomal secretion of cathepsin B; (4) cathepsin B mediates lung cancer cell migration. Here, CTSB is linked to lung cancer.