Perturbation of the tight junction permeability barrier by occludin loop peptides activates beta-catenin/TCF/LEF-mediated transcription

Here we show that interference with the integrity of the transepithelial pe rmeability barrier of mouse mammary epithelial cells by treatment with synt hetic peptides, homologous to the second extracellular domain of occludin, decreased the amount of occludin protein present at tight junctions and led to the formation of multilayered, unpolarized cell clusters. In addition, transcription of the adherens junction protein beta -catenin was induced. F ollowing accumulation of soluble beta -catenin protein, transcription by be ta -catenin/TCF/LEF was increased, as revealed by transcriptional assays fo llowing transient transfection of the reporter construct. Furthermore, trea tment with occludin-II peptides up-regulated RNA levels of the known beta - catenin/TCF/LEF downstream target gene c-myc. The data presented imply a fu nctional cross-talk between tight and adherens junctions that possibly cont ributes to the stepwise transformation during oncogenesis.