Yamada Shin-Ichi, Yanamoto Souichi, Naruse Tomofumi, Matsushita Yuki, Takahashi Hidenori, Umeda Masahiro, Nemoto Takayuki K, Kurita Hiroshi
Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, 390-8621, Japan.
Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Pathol Oncol Res. 2016 Jul;22(3):625-32. doi: 10.1007/s12253-016-0049-6. Epub 2016 Feb 13.
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.
口腔鳞状细胞癌（OSCC）是头颈部最常见的恶性肿瘤，占口腔癌的90%以上。S期激酶相关蛋白2（Skp2）是F盒蛋白家族的成员，也是Skp1-Cullin-F盒蛋白E3泛素连接酶复合物的底物识别亚基。Skp2具有致癌性，在人类癌症中过表达。本研究的目的是确定Skp2在OSCC中的临床病理意义，并阐明其在体外OSCC细胞系中的功能。采用免疫组织化学染色、RT-PCR、蛋白质免疫印迹、迁移和侵袭试验以及siRNA转染等多种方法，以研究Skp2在OSCC中的临床病理意义和分子功能。Skp2的过表达在OSCC中比在正常口腔上皮中更常见。根据T分类、N分类和侵袭模式，在高分级癌症中也更频繁地检测到Skp2过表达。Skp2高表达组的预后明显较差，为30.1%，而低表达组为63.0%。Skp2的下调降低了HSC3细胞的迁移和侵袭能力。此外，Skp2的抑制通过Sp1降低了MMP-2和MMP-9的酶活性。Skp2可能是OSCC患者的一个预后因素，也可能在OSCC细胞的迁移和侵袭能力中发挥关键作用。
