title: MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer.
abstract: BACKGROUND
  Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients' poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients' prognosis.
  
  
  METHODS
  We checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software.
  
  
  RESULTS
  MTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What's more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival.
  
  
  CONCLUSIONS
  We revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Molecular Diagnostics Key Laboratory of Guangdong, Guangdong Medical University, 1 New Town Road, Dongguan, 523808, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Beijing, 100021, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, the First Affiliated Hospital, China Medical University, Shenyang, 110001, China.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, the Affiliated Zhongshan Hospital of Dalian University, 6 Jie Fang Road, Dalian, 116001, China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Xue
authors.affiliation: Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Beijing, 100021, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Beijing, 100021, China.
authors.forename: Xiting
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Clinical Biochemistry, Medical Molecular Diagnostics Key Laboratory of Guangdong, Guangdong Medical University, Dongguan, 523808, China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Liang
authors.affiliation: Department of Thoracic Surgery, the Affiliated Zhongshan Hospital of Dalian University, 6 Jie Fang Road, Dalian, 116001, China. zhilong509@126.com.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Molecular Diagnostics Key Laboratory of Guangdong, Guangdong Medical University, 1 New Town Road, Dongguan, 523808, China. lyj0236@163.com.
authors.forename: YongJun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, 17 Panjiayuan Nanli, Beijing, 100021, China. qianhaili001@163.com.
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011379:Prognosis; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases