title: Fucosylated TGF-β receptors transduces a signal for epithelial-mesenchymal transition in colorectal cancer cells.
abstract: BACKGROUND
  Transforming growth factor-β (TGF-β) is a major inducer of epithelial-mesenchymal transition (EMT) in different cell types. TGF-β-mediated EMT is thought to contribute to tumour cell spread and metastasis. Sialyl Lewis antigens synthesised by fucosyltransferase (FUT) 3 and FUT6 are highly expressed in patients with metastatic colorectal cancer (CRC) and are utilised as tumour markers for cancer detection and evaluation of treatment efficacy. However, the role of FUT3 and FUT6 in augmenting the malignant potential of CRC induced by TGF-β is unclear.
  
  
  METHODS
  Colorectal cancer cell lines were transfected with siRNAs for FUT3/6 and were examined by cell proliferation, invasion and migration assays. The expression and phosphorylation status of TGF-β downstream molecules were analysed by western blot. Fucosylation of TGF-β receptor (TβR) was examined by lectin blot analysis.
  
  
  RESULTS
  Inhibition of FUT3/6 expression by siRNAs suppressed the fucosylation of type I TβR and phosphorylation of the downstream molecules, thereby inhibiting the invasion and migration of CRC cells by EMT.
  
  
  CONCLUSIONS
  Fucosyltransferase 3/6 has an essential role in cancer cell adhesion to endothelial cells by upregulation of sialyl Lewis antigens and also by enhancement of cancer cell migration through TGF-β-mediated EMT.
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Takimoto
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Tamura
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ono
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Murase
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Osuga
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Molecular Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iyama
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyanishi
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Division of Molecular Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kobune
authors.affiliation: 1] Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, Sapporo, Japan [2] Division of Clinical Oncology, Sapporo Medical University Graduate School of Medicine, Sapporo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kato
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D005647:Fucosyltransferases; C019818:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase; C515956:FUT6 protein, human