Psoriasin/S100A7 modulates β-catenin signaling and inhibits tumor growth and progression of oral cavity squamous cell carcinoma

Abstract

Overexpression of psoriasin/S100A7, a small calcium-binding protein, has been associated with the development of psoriasis and carcinomas in different types of epithelia, but its precise functions are still unknown. Using human tissue specimens, cultured cell lines, and a mouse model, we found that psoriasin/S100A7 expression is inversely correlated with Oral Cavity Squamous Cell Carcinoma (OCSCC) tumor invasiveness and malignancy. Specifically, psoriasin/S100A7 is highly expressed in pre-invasive, well-differentiated and early staged-human and mouse OCSCC specimens, but little or no expression was observed in poorly differentiated, invasive tumors. Of interest, the use of an adenoviral-mediated gene expression system revealed that overexpression of psoriasin/S100A7 in OCSCC cell line suppresses the tyrosine phosphorylation of β-catenin, the Epidermal Growth Factor (EGF)-induced disruption of E-cadherin/β-catenin-mediated cell adhesion and c-Myc expression, thereby resulting in cell growth inhibition. Indeed, while down-regulation of psoriasin/S100A7 by small interfering RNA (siRNA) was found to enhance β-catenin signaling, forced psoriasin/S100A7 expression in mouse OCSCC tumors promoted cell differentiation, inhibiting tumor growth, tumor cell dissemination and invasion. Taken together, our results suggest that psoriasin/S100A7 is an important modulator for the β-catenin signaling which plays an important role in Epithelial-mysenchymal Transition (EMT) during tumor progression and that despite psoriasin/S100A7’s overexpression in early-stage OCSCC tumorigenesis, it actually inhibits EMT and tumor progression during the development of OCSCC.