Signaling pathways in anchoring junctions of epithelial cells: cell-to-cell and cell-to-extracellular matrix interactions

Epithelial cells form the epithelium, one of the basic tissues of the human body. These cells present specializations from tissue to tissue, determining different structures and functions. Tissues formed by epithelial cells are characterized by the few extracellular matrix found between adjacent cells. In this way, to preserve tissue integrity, cells have to stick to each other and have to maintain a strict communication with the environment via cell junctions. Signal transduction is the main way of cell communication, being vital for the regulation of cell survival and proliferation. In cell junctions, this communication occurs through cell adhesion molecules that promote cell-to-cell and cell-to-extracellular matrix adhesion, as well as, enable the flow of information to the inside and to the outside of the cell. These molecules include integrins and cadherins, among others. The impairment of cell signaling in epithelial junctions has been involved in several pathological processes that underlie the development of, for example, colorectal cancer. Thus, epithelial cell signaling mediators have been explored as potential therapeutic targets and efforts have been made to achieve a deeper understanding of molecular events that occur at cell junctions. In this review, we address the current knowledge on the main signaling events that take place in anchoring junctions of epithelial cells, focusing both on cell-to-cell and cell-to-matrix interactions. To conclude, we explore some relevant consequences from epithelial cell signaling impairment and demonstrate that the molecular mediators of the pathways analyzed may be putative therapeutic targets.