Fig. 5From: Resistance of HNSCC cell models to pan-FGFR inhibition depends on the EMT phenotype associating with clinical outcomeThe EMT profile is altered most strongly and in opposite directions in sensitive versus resistant HNSCC cell models after FGFR inhibition. A Normalized enrichment score (NES) summary of six gene set enrichment analyses (GSEA) for MSigDB hallmark gene sets. Top 20 hallmarks with the highest variance between DEG comparison groups (n = 4; IR, 6 Gy X-ray irradiated; FGFRi, FGFR inhibitor treatment; FGFRi/IR, combined treatment) are depicted. Significance levels (p.adj, adjusted p-value ≤ 0.05) are indicated by triangle size. Triangle direction represents enrichment or suppression in the corresponding DEG comparison group per cell model. B NES summary graph of multiple GSEA of indicated HNSCC-related EMT gene sets (Table S3) in each DEG comparison group of both cell models. Significance levels (adjusted p-value ≤ 0.05) are indicated by triangle size. Triangle direction represents enrichment or suppression in the corresponding DEG comparison group. C Expression heatmap of selected EMT marker genes in both cell models. Genes are annotated by their corresponding HNSCC gene signatures (Table S3). Columns represent individual biological replicates; rows are clustered hierarchically. D Western blot analysis of selected EMT marker proteins from whole cell lysates of 3D lrECM grown cell models upon indicated treatments. β-actin served as loading control. Representative blots are shown. Where indicated, cells were treated with 2 µM FGFRi (DMSO was used as control). E Densitometric analyses of EMT marker expression shown in ‘D’. Mean fold changes (± standard deviation; n = 3) compared to corresponding non-irradiated/irradiated controls are shown. All samples were normalized to their corresponding β-actin loading control (Two-way ANOVA utilizing normalized densitometry data, Tukey multiple comparison test, **p ≤ 0.01; *p ≤ 0.05)Back to article page