Skp2 Regulates the Expression of MMP-2 and MMP-9, and Enhances the Invasion Potential of Oral Squamous Cell Carcinoma.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck regions and accounts for more than 90% of cancers in the oral cavity. S-phase kinase-associated protein-2 (Skp2) is a member of the F-box protein family and the substrate recognition subunit of the Skp1-Cullin-F box protein E3 ubiquitin ligase complex. Skp2 is oncogenic and overexpressed in human cancers. The aims of the present study were to determine the clinicopathological significance of Skp2 in OSCC and clarify its function in OSCC cell lines in vitro. Multiple methods including immunohistochemical staining, RT-PCR, western blotting, migration and invasion assays, and siRNA transfection were employed in order to investigate the clinicopathological significance and molecular function of Skp2 in OSCC. The overexpression of Skp2 was more frequent in OSCC than in the normal oral epithelium. It was also more frequently detected in cancers with higher grades according to the T classification, N classification, and pattern of invasion. The high-Skp2 expression group had a significantly poorer prognosis, at 30.1%, than that of the low-expression group, at 63.0%. The downregulation of Skp2 decreased migration and invasion potentials in HSC3 cells. Moreover, the suppression of Skp2 reduced the enzyme activities of MMP-2 and MMP-9 via Sp1. Skp2 may be a prognostic factor in OSCC patients, and may also play crucial roles in the migration and invasion potentials of OSCC cells.