The function of cadherin cell adhesion molecules is thought to be regulated by a group of cytoplasmic proteins, including a-catenin. We Identified a subtype of atatenin, termed aN-catenin, which Is associated with N-cadherin and expressed mainly in the nervous system. cDNA transfection experiments showed that aN-catenin can also bind with E-cadherin. To investigate the role of aNtatenin, we transfected lung carcinoma PC9 cells, which express E-cadherln and j3-catenin but neither a-nor aNtatenin, with aN-catenin cDNA. While parental PC9 grew as Isolated cells, the transfectant lines formed aggregates in which cells were tightly adhered to each other, showing epithelial arrangements, and they occasionally gave rise to cystic spheres. These results suggest that aN-catenin is crucial not only for cadherln function but also for organization of multicellular structures.