Subcellular Localization of β-Catenin Is Regulated by Cell Density

Abstract It is generally accepted that subcellular distribution of β-catenin regulates its function. Membrane-bound β-catenin mediates cell–cell adhesion, whereas elevation of the cytoplasmic and nuclear pool of the protein is associated with an oncogenic function. Although the role of β-catenin in transformed cells is relatively well characterized, little is known about its importance in proliferation and cell-cycle control of nontransformed epithelial cells. Using different approaches we show that in human keratinocytes (HaCaT) β-catenin is distributed throughout the cells in subconfluent, proliferating cultures. In contrast, β-catenin is nearly exclusively located at the plasma membrane in confluent, contact-inhibited cells. Hence, we demonstrate for the first time that β-catenin is translocated from the cytoplasm to the plasma membrane in response to high cell density. We conclude that β-catenin plays an important role in proliferation and mediating contact-inhibition by changing intracellular localization.