Credit: Reprinted with permission of AAAS

A potential therapeutic target for skin cancer emerges from a study in the 18 March issue of Science on a rare blistering disorder.

The disorder results from defects in type VII collagen, which helps glue the outer and inner layers of the skin together. The slightest abrasion can cause painful skin blistering in individuals with the disorder, called recessive dystrophic epidermolysis bullosa (RDEB). More than half of RDEB patients also die by age 40 of a more common affliction, squamous cell carcinoma—the second most common cancer in the United States.

Susana Ortiz-Urda et al. asked why some RDEB patients succumb to skin cancer whereas others are spared. Some RDEB patients, they found, retain a small region of the type VII collagen gene that encodes NC1 (the amino-terminal noncollagenous domain). The investigators provide evidence that NC1—through binding to laminin-5—acts as a conduit to promote the invasion of cancerous skin cells into surrounding tissue. Such invasion could be stopped by antibodies to NC1 in animal models.

Shown is skin from a RDEB patient with NC1: NC1 is in red, epithelial cells in green and nuclei in blue.