title: Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer.
abstract: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN.
  
  
  
  The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model.
  
  
  
  Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation.
  
  
  
  The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. © 2016 Wiley Periodicals, Inc. Head Neck 39: 476-485, 2017.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Departments of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Head and Neck Surgery and Otolaryngology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan.
authors.forename: Yasunao
authors.initials: Y
authors.lastname: Kogashiwa
authors.affiliation: Departments of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Yuma
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Partial Denture Prosthodontics, Nihon University School of Dentistry, Kanda, Chiyoda-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shionome
authors.affiliation: Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan, Kanda, Chiyoda-ku, Tokyo, Japan.
authors.forename: Masatake
authors.initials: M
authors.lastname: Asano
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D000068818:Cetuximab / Q000494:pharmacology*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D014183:Transplantation, Heterologous
chemical_list: D000089982:ADP-Ribosylation Factor 6; C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D061067:Antibodies, Monoclonal, Humanized; C512478:EGFR protein, human; D066246:ErbB Receptors; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse; D000068818:Cetuximab
keywords: AMAP1; GEP100; cetuximab; epithelial-mesenchymal transition; head and neck