title: Membrane Type 1 Matrix Metalloproteinase induces an epithelial to mesenchymal transition and cancer stem cell-like properties in SCC9 cells.
abstract: BACKGROUND
  Tissue invasion and metastasis are acquired abilities of cancer and related to the death in oral squamous cell carcinoma (OSCC). Emerging observations indicate that the epithelial-to-mesenchymal transition (EMT) is associated with tumor progression and the generation of cells with cancer stem cells (CSCs) properties. Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) is a cell surface proteinase, which is involved in degrading extracellular matrix components that can promote tumor invasion and cell migration.
  
  
  METHODS
  In the current study, we utilized SCC9 cells stably transfected with an empty vector (SCC9-N) or a vector encoding human MT1-MMP (SCC9-M) to study the role of MT1-MMP in EMT development.
  
  
  RESULTS
  Upon up-regulation of MT1-MMP, SCC9-M cells underwent EMT, in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial markers (E-cadherin, cytokeratin18 and β-catenin) and an increased expression of mesenchymal markers (vimentin and fibronectin). We further demonstrated that MT1-MMP-induced morphologic changes increased the level of Twist and ZEB, and were dependent on repressing the transcription of E-cadherin. These activities resulted in low adhesive, high invasive abilities of the SCC9-M cells. Furthermore, MT1-MMP-induced transformed cells exhibited cancer stem cell (CSC)-like characteristics, such as low proliferation, self-renewal ability, resistance to chemotherapeutic drugs and apoptosis, and expression of CSCs surface markers.
  
  
  CONCLUSIONS
  In conclusion, our study indicates that overexpression of MT1-MMP induces EMT and results in the acquisition of CSC-like properties in SCC9 cells. Our growing understanding of the mechanism regulating EMT may provide new targets against invasion and metastasis in OSCC.
authors.affiliation: Department of Basic Science of Stomatology, Institute of Stomatology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Cong-Chong
authors.initials: CC
authors.lastname: Yang
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Zhu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Xu
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Ning
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Ye
authors.forename: Lai-Kui
authors.initials: LK
authors.lastname: Liu
mesh_terms: D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053538:Keratin-18 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D014411:Neoplastic Stem Cells; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D014157:Transcription Factors / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D005353:Fibronectins; D018398:Homeodomain Proteins; D053538:Keratin-18; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D014746:Vimentin; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051176:beta Catenin; D053511:Matrix Metalloproteinase 14
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