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Fig. 2 | Journal of Experimental & Clinical Cancer Research

Fig. 2

From: FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis

Fig. 2

High-dose MT induces upregulation of FGF19 in HNSCC cells via ATF4. a The effects of high and low dose of MT on the activation of elF2α-ATF4-FGF19 signaling pathway in the indicated cell lines following MT treatment for 12 h. b MTNR1A mRNA levels in HNSCC cell lines and normal oral keratinocytes (hTERT). c, d The effects of high and low dose of MT on the increase of FGF19 levels in the orthotopic mouse tongue tumor model. The xenografts were harvested for western blotting analysis (c) after homogenization and IHC with the anti-FGF19 antibody (d). In (d), arrows indicate FGF19-positive tumor cells in the HN12-derived tumor xenografts. e The protein levels of FGF19 in human primary HNSCC tissues with high or low levels of serum MT determined by IHC. In (d, e), quantitative data are shown in the right panels. f, g The effect of ATF4 knockdown on FGF19 expression in HN12 cells at either protein (f) or mRNA levels (g). h The binding of ATF4 on the FGF19 gene promoter determined by ChIP-qPCR assay. A putative ATF4 binding site (AARE) on the FGF19 gene promoter is shown in the cartoon (above). i The enrichment of ATF4 on the FGF19 gene promoter determined by ChIP-qPCR assay in the presence or absence of 5 mM MT. *p < 0.05; **p < 0.01

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