EGFRvIII Expression and Signaling in head and neck squamous cell carcinoma

摘要: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in United States even more prevalent many developing countries. The mortality rate of ~50% has remained unchanged for decades emphasizing need to increase our understanding HNSCC biology. Overexpression EGFR found up 90% cases been implicated oncogenicity by providing sustained signaling proliferation, anti-apoptosis, angiogenesis metastasis. Cetuximab (an specific monoclonal antibody) was FDA-approved 2006 making it first new treatment 45 years. However, clinical response cetuximab only 10%, indicating better understand mechanisms biology investigate tumor growth presence wtEGFR blockade. An altered form EGFR, EGFRvIII, lacks exons 2-7 a probable mechanism resistance. We previously reported EGFRvIII be expressed ~40% tumors where cells expressing were relatively resistant xenograft models. present study undertaken determine prognostic significance amplification, mRNA protein levels HNSCC. We that phosphorylation status are best indicators patient prognosis. Utilizing Cancer Genome Atlas data samples we expression GBM often DNA or transcriptional aberration but likely splice variant. developed lines utilizing these models vitro vivo, able increases invasion migration via STAT3 knockdown using siRNA decoy abrogated migration. Akt involved EGFRvIII-mediated not invasion. SFKs also migration, specifically Lyn. In vivo significantly inhibited with SFK inhibitor dasatinib.