Unveiling Skin Cancers Pathophysiology via the Modeling of Xeroderma Pigmentosum Disease Using CRISPR-Cas9 Technology

This study explores the pathophysiology of skin cancers associated with Xeroderma pigmentosum group C (XPC) by using CRISPR-Cas9 technology to edit the XPC gene in human skin cells. The research successfully created cellular models using keratinocytes, fibroblasts, and melanocytes to mimic the disease. Proteomic analysis revealed a unique signature of 400 proteins significantly altered in UV-irradiated XPC knockout cells compared to wild-type cells, highlighting a complete dysregulation of the JAK/STAT signaling pathway. This pathway's dysregulation was experimentally validated and suggests that blocking JAK/STAT could mitigate the photosensitive phenotype in XPC cells. Additionally, a 3D reconstructed skin model using XPC knockout cells showed abnormal extracellular matrix remodeling, further enhancing disease modeling.