title: NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway.
abstract: N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however β-catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and β-catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and  β-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression.
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Runna
authors.initials: R
authors.lastname: Ai
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Guo
authors.affiliation: b Division of Medical Biochemistry , Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Lanping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: b Division of Medical Biochemistry , Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town , Cape Town , South Africa.
authors.forename: Denver T
authors.initials: DT
authors.lastname: Hendricks
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D016259:Genes, myc; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D014162:Transfection; D060449:Wnt Signaling Pathway; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: EMT; NDRG1; TLE2; Wnt pathway; esophageal cancer; β-catenin