title: Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Upregulation of metastasis-associated protein 1 (MTA1) has been reported to contribute to the development of esophageal squamous cell carcinoma. Therefore, the objective of our study was to identify the molecular mechanisms of MTA1 underlying the invasion and metastasis of ESCC. We overexpressed MTA1 in ESCC cells to examine the role of MTA1 in the regulation of the cell invasion. In addition, using luciferase reporter assay and electrophoretic mobility shift assays, we evaluated the binding of MTA1 to the promoter of E-cadherin. We found that MTA1 overexpression promotes invasiveness of the human esophageal carcinoma cell line EC-9706. This effect was accompanied by downregulation of the epithelial cell marker E-cadherin and upregulation of vimentin and MMP-9 luciferase reporter assays showed that MTA1 inhibited the promoter activity of E-cadherin and that this was dependent on Snail, Slug and HDAC1. We also found that Snail and Slug bound the E-boxes in the promoter of E-cadherin and recruited MTA1 and HDAC1 to suppress E-cadherin expression, as confirmed by electrophoretic mobility shift and chromatin immunoprecipitation assays. MTA1 promotes tumor invasion by downregulation of E-cadherin. These results demonstrate a novel role for MTA1 in the regulation of esophageal squamous cell carcinoma invasion and provide insight into the mechanisms involved in this process.
authors.affiliation: Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Clinical Medicine, Shanghai Jiaotong University Affiliated Renji Hospital, Shanghai 200127, P.R. China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, P.R. China.
authors.forename: Xinghe
authors.initials: X
authors.lastname: Wang
mesh_terms: D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000235:genetics; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators
chemical_list: D015820:Cadherins; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases