title: Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin.
abstract: OBJECTIVE
  Metastasis-associated protein 2 is considered as an intrinsic subunit of the nucleosome remodelling and histone deacetylase complex, which contributes to the epigenetic silencing genes. More and more evidence suggests that metastasis-associated protein 2 is required to maintain the malignant phenotype, but the role of metastasis-associated protein 2 function in mediating tumour metastasis in non-small-cell lung cancer has not been explored.
  
  
  METHODS
  Bioinformatics was used to detect the GEO 3141 database, the online tool of Kmplot was used to confirm the high expression of metastasis-associated protein 2 in influencing 5-year overall survival. Wound-healing assay, Transwell invasion assay and Living imaging assay together showed that MTA2 shRNA inhibited cell migration and invasion in vitro and in vivo. Chromatin immunoprecipitation, quantitative chromatin immunoprecipitation and luciferase reporter assays showed metastasis-associated protein 2 binding on the promoter of the epithelial transmembrane glycoprotein (Ep-CAM) and cell adhesion molecule E-cadherin.
  
  
  RESULTS
  The patient samples collected in our hospital show that metastasis-associated protein 2 was expressed in aggressive lung cancer cells, and its higher expression is correlated with poor prognosis. Metastasis-associated protein 2 promoted cell migration and invasion in vitro and in vivo through binding on the promoter of Ep-CAM and E-cadherin. Luciferase reporter assays showed repressed or enhanced E-cadherin or Ep-CAM promoter-driven luciferase reporter under metastasis-associated protein 2 overexpression or depletion. The changes in the level of protein and RNA implied that suppression of downstream E-cadherin or Ep-CAM was an important mechanism by which metastasis-associated protein 2 triggered epithelial-mesenchymal transition and metastasis.
  
  
  CONCLUSIONS
  Together, our experiments reveal the mechanism for metastasis-associated protein 2 in facilitating invasive potential of non-small-cell lung cancer cells, suggesting that metastasis-associated protein 2 might be a potential therapeutic target for treating the metastasis of non-small-cell lung cancer.
authors.affiliation: Department of Respiratory Diease, Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Diease, Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Second Affiliated Hospital Zhejiang University College of Medicine, Hangzhou, China binzhangzhejiang@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Shen
mesh_terms: D000951:Antigens, Neoplasm; D015820:Cadherins / Q000037:antagonists & inhibitors*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000556:secondary*; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D000071858:Epithelial Cell Adhesion Molecule; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D015820:Cadherins; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D012097:Repressor Proteins; C120917:MTA2 protein, human; D006655:Histone Deacetylases
keywords: E-cadherin; MTA2; NSCLC, Ep-CAM; metastasis