High-dose melatonin activates the ER stress-associated PERK-eIF2α-ATF4 pathway, leading to upregulation of FGF19 expression in HNSCC cells, promoting FGFR4-Vimentin invasive signaling, attenuating melatonin's ability to suppress metastasis 20 (Figure 5). This evidence concerns the gene FGFR4 and head and neck squamous cell carcinoma.