title: Kindler syndrome in mice and men.
abstract: 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 β-integrin binding protein. Thus far, it has been unclear what specific signaling events occur in KS keratinocytes to promote tumorigenesis, especially since loss of β-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 TGFβ signaling independent of β-integrins. These β1-integrin-independent functions of Kindlin-1 may contribute to the increased SCC risk in KS patients.
authors.affiliation: Department of Dermatology; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Duperret
authors.affiliation: Department of Dermatology; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Ridky
mesh_terms: D000818:Animals; D001768:Blister; D002352:Carrier Proteins / Q000502:physiology*; D049109:Cell Proliferation; D004820:Epidermolysis Bullosa; D015603:Keratinocytes / Q000378:metabolism*; D010510:Periodontal Diseases; D010787:Photosensitivity Disorders; D012867:Skin / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins
keywords: Kindler syndrome; Kindlin-1; TGFβ; Wnt; integrin αv; integrin β1; skin; squamous cell carcinoma