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Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation
- Source :
- Oncogene, Oncogene, vol 29, iss 37
- Publication Year :
- 2010
-
Abstract
- Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors.
- Subjects :
- STAT3 Transcription Factor
EGFRvIII
Cancer Research
Clinical Sciences
Oncology and Carcinogenesis
medicine.disease_cause
Article
STAT3
03 medical and health sciences
0302 clinical medicine
Growth factor receptor
stomatognathic system
Genetics
medicine
otorhinolaryngologic diseases
Humans
Neoplasm Invasiveness
Epidermal growth factor receptor
Oncology & Carcinogenesis
Molecular Biology
neoplasms
030304 developmental biology
0303 health sciences
Cetuximab
biology
Epidermal Growth Factor
Head and neck cancer
Carcinoma
STAT3 and cancer cell invasion
Cell cycle
medicine.disease
Head and neck squamous-cell carcinoma
3. Good health
ErbB Receptors
stomatognathic diseases
Squamous Cell
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Cancer research
biology.protein
Carcinoma, Squamous Cell
cancer cell invasion
head and neck cancer
Carcinogenesis
epidermal growth factor receptor
medicine.drug
Receptor
Subjects
Details
- ISSN :
- 14765594
- Volume :
- 29
- Issue :
- 37
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....32c80f1a27c8f68e22f02355b01371b0