BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9

International Journal of Molecular Sciences

Chou-Kit Chou²  Chang-Yi Wu³  Jeff Yi-Fu Chen⁷  Ming-Chong Ng⁷  Hui-Min David Wang⁸  Jen-Hao Chen⁴  Shyng-Shiou F. Yuan¹  Eing-Mei Tsai⁵  Jan-Gowth Chang⁶  Chien-Chih Chiu⁷ 

[1] Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan; E-Mail:;School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan;Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mails:;Department of Fragrance and Cosmetics Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:

关键词: BubR1;    spindle assembly checkpoint;    oral squamous cancer cell;    migration;    metastasis;   

DOI  :  10.3390/ijms160715104

来源: mdpi

【 摘 要 】

BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC). However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 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 BubR1in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 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 BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.