Cetuximab inhibits oral squamous cell carcinoma invasion and metastasis via degradation of epidermal growth factor receptor

Wei Dai; Yanshu Li; Qing Zhou; Zhongfei Xu; Changfu Sun; Xuexin Tan; Li Lu

doi:10.1111/jop.12116

Cetuximab inhibits oral squamous cell carcinoma invasion and metastasis via degradation of epidermal growth factor receptor

J Oral Pathol Med. 2014 Apr;43(4):250-7. doi: 10.1111/jop.12116. Epub 2013 Sep 11.

Authors

Wei Dai¹, Yanshu Li, Qing Zhou, Zhongfei Xu, Changfu Sun, Xuexin Tan, Li Lu

Affiliation

¹ Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, China.

PMID: 24020947
DOI: 10.1111/jop.12116

Abstract

Cetuximab (Erbitux, C225) is a chimeric monoclonal antibody that binds to the extracellular domain of epidermal growth factor receptor (EGFR), inhibiting tumor growth, invasion, angiogenesis and metastasis. However, the mechanisms underlying the effect of Cetuximab in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that Cetuximab modulates EGFR protein stability through the ubiquitin/proteasome pathway, resulting in the inhibition of human OSCC growth. Cetuximab significantly inhibited the migration and invasion of human OSCC cells by blocking epithelial/mesenchymal transition (EMT) and the AKT and ERK pathways. Furthermore, Cetuximab-inhibited cell growth by modulating the expression of integrin β5. Taken together, these results provide novel insights into the mechanism of Cetuximab action and suggest potential therapeutic strategies for OSCC.

Keywords: Cetuximab; epidermal growth factor receptor; immunoprecipitation; tongue cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actins / antagonists & inhibitors
Antibodies, Monoclonal, Humanized / pharmacology*
Antibodies, Monoclonal, Humanized / toxicity
Carcinoma, Squamous Cell / pathology*
Carcinoma, Squamous Cell / secondary
Cell Culture Techniques
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Cetuximab
Cysteine Proteinase Inhibitors / pharmacology
Epithelial-Mesenchymal Transition / drug effects
ErbB Receptors / antagonists & inhibitors*
Humans
Integrin beta Chains / drug effects
Leupeptins / pharmacology
MAP Kinase Signaling System / drug effects
Neoplasm Invasiveness
Neovascularization, Pathologic / pathology
Oncogene Protein v-akt / antagonists & inhibitors
Proteasome Endopeptidase Complex / drug effects
Protein Processing, Post-Translational / drug effects
Tongue Neoplasms / pathology*
Ubiquitin / drug effects

Substances

Actins
Antibodies, Monoclonal, Humanized
Cysteine Proteinase Inhibitors
Integrin beta Chains
Leupeptins
Ubiquitin
integrin beta5
ErbB Receptors
Oncogene Protein v-akt
Proteasome Endopeptidase Complex
Cetuximab
benzyloxycarbonylleucyl-leucyl-leucine aldehyde