title: Bmi1 drives stem-like properties and is associated with migration, invasion, and poor prognosis in tongue squamous cell carcinoma.
abstract: Bmi1 (B-cell-specific Moloney murine leukemia virus insertion site 1) had been found to involve in self -renewal of stem cells and tumorigenesis in various malignancies. The purpose of this study is to evaluate the role of Bmi1 in the development of tongue squamous cell carcinoma (TSCC) and its functional effect on the migration and invasion of TSCC. Initially, immunohistochemistry revealed that Bmi1 overexpression was a common event in premalignant dysplasia, primary TSCC, and lymph node metastases and was associated with a poor prognosis. A significant correlation between Bmi1 and SOD2 (manganese superoxide dismutase) expression was observed. Side population (SP) cells were used as cancer stem-like cells and further assessed by sphere and colony formation assays, and the expression of stem cell markers. TSCC cells with higher migration and invasion ability (UM1 cell lines) showed a higher proportion of SP cells and Bmi1 expression than TSCC cells with lower migration and invasion ability (UM2 cell lines). Knockdown of Bmi1 in UM1 or SP cells inhibited migration and invasion and decreased the sphere and colony formation, and the expression of stem cell markers and SOD2. Direct binding of C-myc to the Bmi1 promoter was demonstrated by chromatin immunoprecipitation and luciferase assays. Moreover, C-myc knockdown in SP cells inhibited their migration and invasion and decreased the expression of Bmi1 and SOD2. Our results indicate that the deregulation of Bmi1 expression is a frequent event during the progression of TSCC and may have a prognostic value for patients with this disease. The Bmi1-mediated migration and invasion of TSCC is related to cancer stem-like cells and involves the C-myc-Bmi1-SOD2 pathway.
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: He
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Luodan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 2. Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL, 60612-7213, USA. ; 3. Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago, IL, 60612-7213, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 1. Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008156:Luciferases; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D014062:Tongue Neoplasms / Q000235:genetics* / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: C069077:BMI1 protein, human; D008156:Luciferases; D063150:Polycomb Repressive Complex 1
keywords: Bmi1.; Cancer stem-like cell; Tongue squamous cell carcinoma; invasion; migration; prognosis