Fig. 5

Tyrosine kinase inhibitors sensitize Hs578T cells to transcriptional inhibition by THZ531. A Western blot showing protein levels of (phosphorylated) C-terminal domain of RNA polymerase II (Pol2), ERK, Akt, MCL1 and tubulin 24 h after treatment with THZ531 (0.1 µM), lapatinib (3.16 µM), nilotinib (1 µM), rabusertib (1 µM), a combination thereof, or THZ531 (1 µM). Western blot images are representative of three independent experiments. B Number of strongly differentially downregulated (Log2 FC <  − 1, Adjusted p < 0.05) or upregulated (Log2 FC > 1, Adjusted p < 0.05) genes after 8 h of lapatinib (3.16 µM), nilotinib (1 µM), THZ531 (0.1 µM), their combination, or THZ531 (1 µM) treatment as determined by RNA sequencing in Hs578T cells. C Overlap of strongly down- and upregulated genes between combination treatments with THZ531 (0.1 µM) and high dose THZ531 (1 µM). D Heatmap showing unsupervised clustering of Log2 FCs of the differentially expressed genes (Log2 FC <  − 0.5/> 0.5, adjusted p < 0.05) in one of the conditions. E Enrichment score and − log10 FDR p values of gene ontology pathway enrichment of ranked Log2 FC upon combination treatment with lapatinib (3.16 µM) and THZ531 (0.1 µM). F Heatmap showing unsupervised clustering of Log2 FC of strongly differentially expressed (Log2 FC > 1 or <  − 1, adjusted p < 0.05) DNA damage genes in one of the conditions. All shown data are from RNA sequencing analysis performed on samples derived in three independent experiments