title: N-myc downstream-regulated gene 1 downregulates cell proliferation, invasiveness, and tumorigenesis in human oral squamous cell carcinoma.
abstract: Oral squamous cell carcinoma (OSCC) is the most common phenotype of oral cancer. N-myc downstream regulated gene 1 (NDRG1) is a modulator for cell proliferation, differentiation, and invasion. The role and function of NDRG1 in OSCC cells remain inconclusive. The (3)H-thymidine incorporation and in vitro matrigel invasion assays revealed NDRG1-knockdown significantly enhanced OSCC cell proliferation and invasion. Overexpressed NDRG1 arrested the cell cycle at the S-phase, thus attenuated cell proliferation in OECM-1 cells. The NDRG1-knockdown enhanced tumorigenesis of OECM-1 cells in the xenograft animal model. Western-blot and zymographic assays revealed that NDRG1 downregulated the gelatinase activities and protein levels of metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). NDRG1 modulated epithelial-mesenchymal transition (EMT) through upregulation of the E-cadherin expression, but downregulation of the N-cadherin, Vimentin, Snail-1, and Slug. Immunofluorescence staining indicated knockdown of NDRG1 enhanced F-actin expression and polymerization. Our results indicated NDRG1 attenuated OSCC cell growth in vitro and in vivo. The downregulation of EMT, MMP-2, and MMP-9 may explain the role of anti-invasion of NDRG1 in human OSCC cells. The experiments recognize that NDRG1 is an antitumor gene in OSCC cells.
authors.affiliation: Department of Otolaryngology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jehn-Chuan
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Collage of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chung
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: School of Nursing, Collage of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan.
authors.forename: Tsui-Hsia
authors.initials: TH
authors.lastname: Feng
authors.affiliation: Department of Anatomy, Collage of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan. Electronic address: hhj143@mail.cgu.edu.tw.
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D000077195:Squamous Cell Carcinoma of Head and Neck; D015854:Up-Regulation; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D015820:Cadherins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: EMT; Invasion; MMP-2; MMP-9; NDRG1; OSCC