A Transcriptomic Map of EGFR-induced Epithelial-to-Mesenchymal Transition Identifies Prognostic and Therapeutic Targets for Head and Neck Cancer

Purpose: We aim to identify transcriptomic changes associated with EGFR-mediated epithelial to mesenchymal transition in carcinoma cells of the upper aerodigestive tract Method: Kyse30 and FaDu (ATCC, Manassas, VA, USA) were passaged in DMEM or RPMI, 10% FCS, 1% penicillin/streptomycin, 5% CO2 atmosphere at 37°C. Treatment with EGF (PromoCell PromoKine, Heidelberg, Germany), EpEX-Fc (Pan et al. PMID: 30261040) were conducted under serum-free conditions for 6h and 72h. Results: Kyse30 cells: At 6h/72h of treatment high-dose EGF (9nM) induced 612/1208 genes; low-dose EGF (1.8nM) induced 397/0 genes; EpEX-Fc (50nM) induced 137/2 genes; high-dose EGF (9nM) + EpEX (50nM) induced 291/0 genes FaDu cells: At 6h/72h of treatment high-dose EGF (9nM) induced 994/1536 genes; low-dose EGF (1.8nM) induced 671/4 genes; EpEX-Fc (50nM) induced 36/0 genes; high-dose EGF (9nM) + EpEX (50nM) induced 911/103 genes Conclusion: High- and low-dose EGF treatment in Kyse30 and FaDu cells differ with respect to short-term and long-term gene regulation. High-dose EGF, which is associated with induction of EMT, induces a higher number of differentially regulated genes (DEGs) after 6h and has a sustained strong regulatory capacity at 72h, when other treatmernts showed no DEGs. Overall design: RNAseq analysis of human Kyse30 and FaDu cell lines treated with different concentrations of EGF and the extracellular domain of EpCAM termed EpEX as a fusion with Fc (EpEX-Fc)