Fig. 2
MEKi resistance is accompanied by a phenotypic switch. A GSEA of RNA-seq from parental compared to resistant cells revealed enriched hallmarks of EMT. B–E Significantly decreased CDH1 (B) and increased CDH2 (D) protein expression assessed by Simple Western (p < 0.05, two-tailed paired Student’s t test on the log2 transformed ratios) and corresponding immunofluorescence of one representative example (cell line #3) (C, E). Either CDH1 (green) or CDH2 (orange) were stained together with DAPI (blue) nuclear staining (scale bars: 50 μm). F Hierarchical clustering of parental and resistant cells based on the metagenes for the pancreatic progenitor and the squamous subtype as defined by Bailey et al. [27]. G GSEA of metagenes defining the pancreatic progenitor or the classical subtype as defined by Bailey et al. [27] (left), Moffitt et al. [29] (middle) or Collisson et al. [28] (right). H Hierarchical clustering like in (F) including P5 and P12 samples. I, J Normalized CDH1 (I) or CDH2 protein expression (J) in four matched parental, resistant, P5 and P12 samples measured by Simple Western, respectively