Deletion of Vitamin D Receptor and Calcium-Sensing Receptor in Keratinocytes Promotes Epidermal Tumorigenesis by Limiting DNA Repair and Oxidative Stress Response Genes

March 2026 in “ The Journal of Steroid Biochemistry and Molecular Biology ”

Yuko Oda, Mark B. Meyer, Iwei Yeh, Zhiyun Lin, Christian T. Wong, Dennis Oh, Daniel D. Bikle

vitamin D receptor calcium-sensing receptor keratinocytes alopecia squamous cell carcinoma oxidative stress DNA repair Xpc Gadd45a UVB-induced damage epidermal stem cells hair follicle stem cells Vdr Casr skin cancer hair loss skin cells sun damage

TLDR Deleting vitamin D and calcium receptors in skin cells increases skin cancer risk by reducing DNA repair and stress response.

The study investigates the effects of deleting both the vitamin D receptor (Vdr) and calcium-sensing receptor (Casr) in keratinocytes, which leads to alopecia and delayed wound healing. In DKO mice, this deletion results in spontaneous development of squamous cell carcinoma as they age. The research identifies oxidative stress as a key pathway affected by the loss of Vdr/Casr, with reduced expression of oxidative stress response and DNA repair genes, such as Xpc and Gadd45a, in keratinocytes. This deficiency impairs the cells' ability to handle oxidative stress and repair DNA, prolonging UVB-induced damage and predisposing epidermal and hair follicle stem cells to malignant transformation.