Type VII Collagen Deficiency in the Oncogenesis of Cutaneous Squamous Cell Carcinoma in Dystrophic Epidermolysis Bullosa
Andrew P. South, Martin Laimer, Mouhamed Gueye, Jennifer Y. Sui, Lawrence F. Eichenfield, Jemima E. Mellerio, Alexander Nyström
Abstract
Dystrophic epidermolysis bullosa is a rare genetic skin disorder caused by COL7A1 sequence variations that result in type VII collagen deficits and cutaneous and extracutaneous manifestations. One serious complication of dystrophic epidermolysis bullosa is cutaneous squamous cell carcinoma, a leading driver of morbidity and mortality, especially among patients with recessive dystrophic epidermolysis bullosa. Type VII collagen deficits alter TGFβ signaling and evoke multiple other cutaneous squamous cell carcinoma progression-promoting activities within epidermal microenvironments. This review examines cutaneous squamous cell carcinoma pathophysiology in dystrophic epidermolysis bullosa with a focus on known oncogenesis pathways at play and explores the idea that therapeutic type VII collagen replacement may reduce cutaneous squamous cell carcinoma risk.