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. 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)