Our results show decreased levels of both phosphorylated EGFR, and total EGFR following EphB4-siRNA transfection and radiation exposure in MSK-921 cells, suggesting that functional interaction between the EphB4 receptor and EGFR might be responsible for promoting tumorigenesis and progression in HNSCC cells. The gene discussed is EPHB4; the disease is head and neck squamous cell carcinoma.