RSPO1-Mutated Keratinocytes From Palmoplantar Keratoderma Display Impaired Differentiation and Invasiveness: Implications for Squamous Cell Carcinoma Susceptibility in Patients With 46XX Disorder of Sexual Development
July 2022
in “
Orphanet journal of rare diseases
”
TLDR RSPO1 mutations in certain patients lead to skin cells that don't develop properly and are more likely to become invasive, increasing the risk of skin cancer.
The study examined the role of R-spondin (RSPO1) proteins in skin conditions, specifically palmoplantar keratoderma (PPK) and squamous cell carcinoma (SCC). The research focused on keratinocytes (skin cells) from a patient with RSPO1 mutations. The findings revealed that these RSPO1-mutated keratinocytes showed impaired differentiation, alterations in cell-cell adhesion, an epithelial-to-mesenchymal transition (EMT)-like phenotype, and invasive properties. The study also found that normal human control plantar fibroblasts could not revert the EMT-like phenotype of PPK keratinocytes, and RSPO1-mutated PPK fibroblasts promoted the dedifferentiation process and invasiveness of control plantar keratinocytes. The study concluded that RSPO1 mutations disrupt the balance between cell proliferation and differentiation, potentially increasing susceptibility to SCC. The research also suggested that Wnt-5a could be a potential therapeutic target for counteracting the EMT-like phenotype.
