Inhibition of epithelial–mesenchymal transition by cetuximab via the EGFR‐GEP100‐Arf6‐AMAP1 pathway in head and neck cancer
Copyright policy )Inhibition of epithelial–mesenchymal transition by cetuximab via the EGFR‐GEP100‐Arf6‐AMAP1 pathway in head and neck cancer
AbstractBackgroundDespite 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.MethodsThe 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.ResultsCetuximab 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.ConclusionThe 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
- Nihon Bunka University Japan
- Saitama Medical University Japan
- Nihon University Japan
- Kyorin University Japan
Mice, Inbred BALB C, Epithelial-Mesenchymal Transition, ADP-Ribosylation Factors, Blotting, Western, Cetuximab, Mice, Nude, Antibodies, Monoclonal, Humanized, ErbB Receptors, Disease Models, Animal, Mice, ADP-Ribosylation Factor 6, Cell Movement, Head and Neck Neoplasms, Cell Line, Tumor, Carcinoma, Squamous Cell, Animals, Humans, Female, Adaptor Proteins, Signal Transducing, Cell Proliferation
Mice, Inbred BALB C, Epithelial-Mesenchymal Transition, ADP-Ribosylation Factors, Blotting, Western, Cetuximab, Mice, Nude, Antibodies, Monoclonal, Humanized, ErbB Receptors, Disease Models, Animal, Mice, ADP-Ribosylation Factor 6, Cell Movement, Head and Neck Neoplasms, Cell Line, Tumor, Carcinoma, Squamous Cell, Animals, Humans, Female, Adaptor Proteins, Signal Transducing, Cell Proliferation
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