title: BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9.
abstract: 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 BubR1 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 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 BubR1 in 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 BubR1 in 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.
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan. fatchou1988@hotmail.com.|Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. fatchou1988@hotmail.com.
authors.forename: Chou-Kit
authors.initials: CK
authors.lastname: Chou
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. cywu@mail.nsysu.edu.tw.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yifuc@kmu.edu.tw.
authors.forename: Jeff Yi-Fu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. mincong2000@gmail.com.
authors.forename: Ming-Chong
authors.initials: MC
authors.lastname: Ng
authors.affiliation: Department of Fragrance and Cosmetics Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. davidw@kmu.edu.tw.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan. davidw@kmu.edu.tw.
authors.forename: Hui-Min David
authors.initials: HM
authors.lastname: Wang
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. jehach@kmu.edu.tw.
authors.forename: Jen-Hao
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yuanssf@ms33.hinet.net.|Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yuanssf@ms33.hinet.net.
authors.forename: Shyng-Shiou F
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. tsaieing@kmu.edu.tw.
authors.forename: Eing-Mei
authors.initials: EM
authors.lastname: Tsai
authors.affiliation: Epigenome Research Center, China Medical University Hospital, Taichung 404, Taiwan. d6781@mail.cmuh.org.tw.|Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan. d6781@mail.cmuh.org.tw.|Department of Laboratory Medicine, China Medical University Hospital, Taichung 404, Taiwan. d6781@mail.cmuh.org.tw.
authors.forename: Jan-Gowth
authors.initials: JG
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. cchiu@kmu.edu.tw.|Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.|Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan. cchiu@kmu.edu.tw.
authors.forename: Chien-Chih
authors.initials: CC
authors.lastname: Chiu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: BubR1; metastasis; migration; oral squamous cancer cell; spindle assembly checkpoint