title: Moesin regulates the motility of oral cancer cells via MT1-MMP and E-cadherin/p120-catenin adhesion complex.
abstract: OBJECTIVE
  The present study aimed to clarify the role of Moesin in oral squamous cell carcinoma (OSCC) progression, especially in regulation of cell motility.
  
  
  METHODS
  Immunohistochemistry and western blotting were used to investigate the expression of Moesin, E-cadherin, p120-catenin and MT1-MMP in normal epithelia, dysplasia and OSCCs. Then, Moesin was knockdown by siRNA in OSCC cell lines, WSU-HN6 and CAL27, and the biological role of Moesin in cell adhesion and motility was evaluated by transwell system, cell spreading and aggregation assays. The interactions between Moesin, MT1-MMP and E-cadherin/p120-catenin complex were determined by co-immunoprecipitation and immunofluorescence.
  
  
  RESULTS
  Moesin expression was found decreased in the membrane and increased in cytoplasm during the malignant transformation of oral epithelia, and cytoplasmic overexpression of Moesin correlated with nodal metastasis and poor prognosis of OSCCs. Furthermore, Moesin-silencing induced an increased cell-cell adhesion but decreased invasiveness, which was subsequently demonstrated might due to Moesin-mediated E-cadherin and p120-catenin interaction. Meantime, Moesin-silencing significantly down-regulated MT1-MMP expression, accompanied by reduced cell motility and impaired filopodia formation, which was also observed when MT1-MMP knockdown by RNAi or tissue inhibitor (TIMP2), indicating the involvement of MT1-MMP in Moesin-mediated cell motility. Finally, the relationship between Moesin, E-cadherin and MT1-MMP was confirmed in OSCC tissue samples.
  
  
  CONCLUSIONS
  Taken together, our results indicate Moesin may regulate cell motility through its interactions with MT1-MMP and E-cadherin/p120-catenin adhesion complex and cytoplasmic expression of Moesin correlates with nodal metastasis and poor prognosis of OSCCs, indicating Moesin may be a potential candidate for targeted gene therapy for OSCCs.
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Avenue Zhongguancun, Haidian District, Beijing 100081, PR China.
authors.forename: Yao-yin
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Avenue Zhongguancun, Haidian District, Beijing 100081, PR China. Electronic address: zhoucx2008@126.com.
authors.forename: Chuan-Xiang
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Avenue Zhongguancun, Haidian District, Beijing 100081, PR China. Electronic address: gaoyan0988@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D051177:Catenins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000502:physiology*; D009062:Mouth Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D008840:Microfilament Proteins; C071058:moesin; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D000095002:Delta Catenin; C000722347:CTNND1 protein, human
keywords: Cell motility; E-cadherin/p120-catenin; MT1-MMP; Moesin; Oral squamous cell carcinoma