title: 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.
authors.affiliation: Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan. yshinshin@shinshu-u.ac.jp.|Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. yshinshin@shinshu-u.ac.jp.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Naruse
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsushita
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umeda
authors.affiliation: Department of Oral Molecular Biology, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takayuki K
authors.initials: TK
authors.lastname: Nemoto
authors.affiliation: Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurita
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D014162:Transfection / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D044786:S-Phase Kinase-Associated Proteins; D025521:Tumor Suppressor Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Skp2; invasion; metastasis; migration; oral squamous cell carcinoma