Desmosomes are specialized structures of the cell membrane that are crucial for the establishment and maintenance of cell-cell adhesion and tissue integrity. Transmembrane proteins of desmosomes, desmogleins, and desmocollins are responsible for extracellular binding and, thus, are important for interkeratinocyte cohesion. Desmoglein 3 (DSG3)
is a member of the desmoglein subfamily of cadherin cell adhesion molecule superfamily. It is mainly expressed in stratified epithelia, including the basal and suprabasilar epidermal layers and throughout the oral epithelium layers. In the human autoimmune blistering disease pemphigus vulgaris, autoantibodies against DSG3 cause loss of cell-cell adhesion (acantholysis) with resultant epidermal and mucosal blisters. More recently, a potential role of desmosomes in cancer development has been hypothesized. To this regard, several investigations have focused on the possible contribution of DSG3 in carcinogenesis. In this article, the role of DSG3 in the process of squamous cell carcinogenesis and the controversies concerning this issue will be discussed.