The desmosomal proteins that underpin desmosomes have been linked to various aspects of epithelial morphogenesis and the establishment of tissue architecture particularly in stratified epithelia. Now Donna Brennan and colleagues investigate the isoform-specific functions of desmosomal cadherin desmoglein 2 (Dsg2) in epidermal biology (see ). The authors generated transgenic mice expressing Dsg2 under the control of the involucrin promoter, which restricts expression to the differentiating cell layers of the skin. These mice exhibit extensive epidermal hyperplasia associated with increased proliferation of the basal and suprabasal epithelial layers. Increased epidermal proliferation is coupled with increased activation of the PI3K/Akt, MAPK, STAT3 and NFκB signalling pathways, which are often associated with increased growth rate. In addition Dsg2 expression confers resistance to anoikis through NFκB activation. Furthermore the authors show that the Dsg2 transgenic mice develop papilloma-like lesions and are more susceptible to chemical carcinogenesis. This study highlights an unrecognised aspect of Dsg2 function in epidermal biology and supports a role for the protein in epithelial malignant transformation
