ONCOmmunity

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

By: Yoshifumi Matsumoto, Hiroyuki Sakurai, Yasunao Kogashiwa, Toru Kimura, Yuma Matsumoto, Takashi Shionome, Masatake Asano, Koichiro Saito, Naoyuki Kohno

Department of Otolaryngology, Head and Neck Surgery, Kyorin University School of Medicine, Tokyo, Japan.
2015-12-29; doi: 10.1002/hed.24626

Abstract

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, 2016.