Inhibition of epithelial–mesenchymal transition by cetuximab via the EGFR‐GEP100‐Arf6‐AMAP1 pathway in head and neck cancer

Background 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. Methods 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. Results 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. Conclusion 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