title: RNAi-mediated gene silencing of ST6GalNAc I suppresses the metastatic potential in gastric cancer cells.
abstract: BACKGROUND
  ST6GalNAc I is a sialyltransferase controlling the expression of sialyl-Tn antigen (STn), which is overexpressed in several epithelial cancers, including gastric cancer, and is highly correlated with cancer metastasis. However, the functional contribution of ST6GalNAc I to development or progression of gastric cancer remains unclear. In this study, we investigated the effects of suppression of ST6GalNAc I on gastric cancer in vitro and in vivo.
  
  
  METHODS
  Gastric cancer cell lines were transfected with ST6GalNAc I siRNA and were examined by cell proliferation, migration, and invasion assays. We also evaluated the effect of ST6GalNAc I siRNA treatment in a peritoneal dissemination mouse model. The differences in mRNA levels of selected signaling molecules were analyzed by polymerase chain reaction (PCR) arrays associated with tumor metastasis in MKN45 cells. The signal transducer and activator of transcription 5b (STAT5b) signaling pathways that reportedly regulate the insulin-like growth factor-1 (IGF-1) were analyzed by Western blot.
  
  
  RESULTS
  ST6GalNAc I siRNA inhibited gastric cancer cell growth, migration, and invasion in vitro. Furthermore, intraperitoneal administration of ST6GalNAc I siRNA- liposome significantly inhibited peritoneal dissemination and prolonged the survival of xenograft model mice with peritoneal dissemination of gastric cancer. PCR array confirmed that suppression of ST6GalNAc I caused a significant reduction in expression of IGF-1 mRNA. Decreased IGF-1 expression in MKN45 cells treated with ST6GalNAc I siRNA was accompanied by reduced phosphorylation of STAT5b.
  
  
  CONCLUSIONS
  ST6GalNAc I may regulate the gene expression of IGF-1 through STAT5b activation in gastric cancer cells and may be a potential target for treatment of metastasizing gastric cancer.
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Fumito
authors.initials: F
authors.lastname: Tamura
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Osuga
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okagawa
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Uemura
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Arihara
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Murase
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iyama
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kohichi
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Miyanishi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kobune
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Rishu
authors.initials: R
authors.lastname: Takimoto
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan. jkato@sapmed.ac.jp.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
mesh_terms: D000818:Animals; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000556:secondary; D034622:RNA Interference; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; C055491:sialosyl-Tn antigen; D007334:Insulin-Like Growth Factor I; D012799:Sialyltransferases; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase
keywords: Gastric cancer; Peritoneal dissemination; ST6GalNAc I; STAT5b; STn