BubRl acts as a promoter in cellular motility of human oral squamous cancer cells through regulating MMP-2 and MMP-9

Abstract

BubRl is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubRl was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC). However, the effect of BubRl on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubRl in the progression of OSCC and confirm the expression of BubRl in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubRl was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK) and human gingival fibroblasts (HGF). Moreover, the expression of BubRl in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubRl was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubRl knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubRl knockdown Ca9-22 cells, suggesting the role of BubRl in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubRl could be a prognostic index in OSCC patients.