Tight junctions are components of the junctional complex linking neighbouring epithelial cells and are important for barrier formation. Recent evidence suggests that tight junctions also participate in signal transduction mechanisms that regulate epithelial cell proliferation, gene expression, differentiation and morphogenesis. One important class of tight-junction-associated signal transduction mechanism is based on dual localisation of certain proteins both at junctions and in the nucleus. These proteins and their partners participate in various steps of gene expression, ranging from regulation of transcription and chromatin structure to mRNA processing and translation. In cancer tissues, their expression is often deregulated in a manner that suggests that tight junctions function as suppressors of proliferation and transformation.