biostudies-literatureDellambra EAssociazione Italiana per la Ricerca sul CancroMinistero della SaluteTelethon275https://www.ebi.ac.uk/biostudies/studies/S-EPMC9295301biostudies-literatureUnknown17(1)<h4>Background</h4>Secreted R-spondin (RSPO) proteins play a key role in reproductive organ development, epithelial stem cell renewal and cancer induction by reinforcing canonical Wnt signaling. We have previously reported that palmoplantar keratoderma (PPK), predisposition to cutaneous squamous cell carcinoma (SCC) development and sex reversal segregate as autosomal recessive trait in patients carrying RSPO1-mutations. Although our previous findings suggested that RSPO1 secreted from fibroblasts regulates keratinocyte growth or differentiation, the role of this protein in the epidermis remains largely unexplored. Our study was aimed at expanding the phenotypic, molecular and functional characterization of RSPO1-mutated skin and keratinocytes.<h4>Results</h4>Cultured primary keratinocytes Orphanet journal of rare diseasesRSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development.PMC9295301Grant Number GGP06252Ricerca Corrente e 5x1000 2013Grant 2007-4093Bondanza SCastiglia DTeson MDellambra ENicodemi EMCondorelli AGDidona BGuerra LCamerino GDelle Monache FCordisco SfalseRSPO1-mutated keratinocytes from palmoplantar keratoderma display impaired differentiation, alteration of cell-cell adhesion, EMT-like phenotype and invasiveness properties: implications for squamous cell carcinoma susceptibility in patients with 46XX disorder of sexual development.<h4>Background</h4>Secreted R-spondin (RSPO) proteins play a key role in reproductive organ development, epithelial stem cell renewal and cancer induction by reinforcing canonical Wnt signaling. We have previously reported that palmoplantar keratoderma (PPK), predisposition to cutaneous squamous cell carcinoma (SCC) development and sex reversal segregate as autosomal recessive trait in patients carrying RSPO1-mutations. Although our previous findings suggested that RSPO1 secreted from fibroblasts regulates keratinocyte growth or differentiation, the role of this protein in the epidermis remains largely unexplored. Our study was aimed at expanding the phenotypic, molecular and functional characterization of RSPO1-mutated skin and keratinocytes.<h4>Results</h4>Cultured primary keratinocytes 2022-01-01T00:00:00Z2022 Jul2025-04-06T19:45:28.196Z2025-04-06T19:45:28.196ZS-EPMC92953013585436310.1186/s13023-022-02434-2