Kindler syndrome in mice and men.

Kindler syndrome (KS) in humans is a severe skin blistering disease associated with inflammation and increased risk of epidermal squamous cell carcinoma (SCC). This disease is known to be caused by loss-of-function mutations in Kindlin-1, a focal adhesion beta-integrin binding protein. Thus far, it has been unclear what specific signaling events occur in KS keratinocytes to promote tumorigenesis, especially since loss of beta-integrins and focal adhesion complexes has been previously shown to prevent or delay tumor formation. In the April issue of Nature Medicine, Rognoni and colleagues generate a transgenic mouse lacking Kindlin-1 in the epidermis to model the key features of KS, and show that Kindlin-1 regulates Wnt and TGFbeta signaling independent of beta-integrins. These beta1-integrin-independent functions of Kindlin-1 may contribute to the increased SCC risk in KS patients.