The role and mechanism of claudins in cancer

Claudins are a tetraspan membrane protein multigene family that plays a structural and functional role in constructing tight junctions. Claudins perform crucial roles in maintaining cell polarity in epithelial and endothelial cell sheets and controlling paracellular permeability. In the last two decades, increasing evidence indicates that claudin proteins play a major role in controlling paracellular permeability and signaling inside cells. Several types of claudins are dysregulated in various cancers. Depending on where the tumor originated, claudin overexpression or underexpression has been shown to regulate cell proliferation, cell growth, metabolism, metastasis and cell stemness. Epithelial-to-mesenchymal transition is one of the most important functions of claudin proteins in disease progression. However, the exact molecular mechanisms and signaling pathways that explain why claudin proteins are so important to tumorigenesis and progression have not been determined. In addition, claudins are currently being investigated as possible diagnostic and treatment targets. Here, we discuss how claudin-related signaling pathways affect tumorigenesis, tumor progression, and treatment sensitivity.