title: Cetuximab inhibits oral squamous cell carcinoma invasion and metastasis via degradation of epidermal growth factor receptor.
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.
authors.affiliation: Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zhongfei
authors.initials: Z
authors.lastname: Xu
authors.forename: Changfu
authors.initials: C
authors.lastname: Sun
authors.forename: Xuexin
authors.initials: X
authors.lastname: Tan
authors.forename: Li
authors.initials: L
authors.lastname: Lu
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000556:secondary; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D039641:Integrin beta Chains / Q000187:drug effects; D007976:Leupeptins / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014062:Tongue Neoplasms / Q000473:pathology*; D025801:Ubiquitin / Q000187:drug effects
chemical_list: D000199:Actins; D061067:Antibodies, Monoclonal, Humanized; D015853:Cysteine Proteinase Inhibitors; D039641:Integrin beta Chains; D007976:Leupeptins; D025801:Ubiquitin; C084344:integrin beta5; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; D046988:Proteasome Endopeptidase Complex; D000068818:Cetuximab; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Cetuximab; epidermal growth factor receptor; immunoprecipitation; tongue cancer