title: Numb Expression Contributes to the Maintenance of an Undifferentiated State in Human Epidermis.
abstract: The epidermis is a stratified epithelium with a stem cell subpopulation in the basal layer that constantly replicates and periodically detaches from the base, undergoing a differentiation process that involves various developmental signals and regulatory pathways. During the last 10 years, a number of studies tried to elucidate the intricate scenario that maintains the epithelial shield during the entire life span. In our study, we investigated the role of Numb in the skin compartment and, in particular, its involvement in stem cell maintenance. Numb expression in the skin compartment was assessed by immunofluorescence and immunohistochemistry analysis. We evaluated Numb expression in primary epithelial cells at various differentiative stages. Moreover, we overexpressed Numb in the isolated population enriched for undifferentiated progenitors to establish its involvement in in vitro differentiation. We demonstrated that Numb in high-proliferating epithelial undifferentiated progenitors contributes to the maintenance of an undifferentiated state. This regulation involves the E3 ligases Itch binding. Moreover, the analysis of a cohort of cutaneous carcinomas showed that Numb is highly expressed in squamous cell carcinoma (SCC), where we observed a direct correlation between the expression of Numb and Ki-67. Our data indicate for the first time that Numb is involved in the maintenance of the undifferentiated proliferating stem cell pool in the epithelial basal layer and its expression could become a new marker in skin cancer.
authors.affiliation: Fondazione Ri.MED, Regenerative Medicine and Biomedical Technologies Unit, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS-ISMETT, Palermo, Italy.
authors.forename: Gioacchin
authors.initials: G
authors.lastname: Iannolo
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Sciuto
authors.forename: Simona
authors.initials: S
authors.lastname: Buccheri
authors.forename: Cristina
authors.initials: C
authors.lastname: Colarossi
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Memeo
authors.forename: Pier Giulio
authors.initials: PG
authors.lastname: Conaldi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000502:physiology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins