The KAI1/CD82 protein has been documented as the tumor metastasis suppressor in many types of human cancers. KAI1/CD82 regulates cell motility and invasiveness; however, the mechanism by which this occurs remains to be fully established. Several studies have shown that KAI1/CD82 modulates integrin-dependent signaling. It was suggested that KAI1/CD82 might function to attenuate the beta 1 integrin function of inducing cellular migration. A wound-healing and modified Boyden chamber assays were performed to investigate the mechanism of the KAI1/CD82-mediated inhibition of cell migration. It was found that the migratory ability of H1299/CD82 was inhibited. The immunoblotting and biotinylation assays revealed that H1299/CD82 showed significantly decreased expression of the mature form of PI, which was functional at the cell surface. It was confirmed that KAI1/CD82 regulates the maturation of the beta 1 integrin using CD82-specific si-RNA. These results support a model in which KAI1/CD82 attenuates the maturation of the beta 1 integrin precursor and thereby suppresses cell migration. (c) 2007 Elsevier Inc. All rights reserved.