Cell adhesion signals regulate the nuclear receptor activity

Significance Cell adhesion is indispensable for multicellular organisms to form cohesive sheets and to serve as tissues and organs. In addition to the adhesive activity, it exhibits the signaling ability to organize a variety of cellular processes. However, the mechanism by which the cell adhesion signaling influences the cellular events, especially on regulation of gene expression, remains obscure. We determine that the cell adhesion signaling originated from the tight-junction protein claudin-6, which targets members of the nuclear receptor superfamily, such as retinoic acid receptor γ and estrogen receptor α, thereby regulating expression of the respective target genes. This signaling provides insight into regulation of nuclear receptor activity by cell adhesion.