title: Claudin 1 mediates tumor necrosis factor alpha-induced cell migration in human gastric cancer cells.
abstract: OBJECTIVE
  To investigate the role of claudin 1 in the regulation of genes involved in cell migration and tumor necrosis factor alpha (TNF-α)-induced gene expression in human gastric adenocarcinoma cells.
  
  
  METHODS
  Knockdown experiments were conducted with claudin 1 small interfering RNA (siRNA), and the effects on the cell cycle, apoptosis, migration and invasion were analyzed in human gastric adenocarcinoma MKN28 cells. The gene expression profiles of cells were analyzed by microarray and bioinformatics.
  
  
  RESULTS
  The knockdown of claudin 1 significantly inhibited cell proliferation, migration and invasion, and increased apoptosis. Microarray analysis identified 245 genes whose expression levels were altered by the knockdown of claudin 1. Pathway analysis showed that the top-ranked molecular and cellular function was the cellular movement related pathway, which involved MMP7, TNF-SF10, TGFBR1, and CCL2. Furthermore, TNF- and nuclear frctor-κB were the top-ranked upstream regulators related to claudin 1. TNF-α treatment increased claudin 1 expression and cell migration in MKN28 cells. Microarray analysis indicated that the depletion of claudin 1 inhibited 80% of the TNF-α-induced mRNA expression changes. Further, TNF-α did not enhance cell migration in the claudin 1 siRNA transfected cells.
  
  
  CONCLUSIONS
  These results suggest that claudin 1 is an important messenger that regulates TNF-α-induced gene expression and migration in gastric cancer cells. A deeper understanding of these cellular processes may be helpful in establishing new therapeutic strategies for gastric cancer.
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiozaki
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Konishi
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iitaka
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakashima
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Nako
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Atsushi Shiozaki, Hiroki Shimizu, Daisuke Ichikawa, Hirotaka Konishi, Shuhei Komatsu, Takeshi Kubota, Hitoshi Fujiwara, Kazuma Okamoto, Daisuke Iitaka, Shingo Nakashima, Yoshito Nako, Eigo Otsuji, Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha
keywords: Cell migration; Claudin 1; Gene expression change; Microarray; Tumor necrosis factor alpha