Fig. 4.

Upregulation of JAK-STAT signalling pathway in HSP90i-resistant clones. a Upregulation of genes involved in JAK-STAT signalling pathway. Heatmap represents the significantly upregulated genes involved in the JAK-STAT signalling pathway in HSP90i-resistant clones CR2 and CR3 compared to parental Hs578T cells. The colour scale indicates the significant log2 FC (q-value ≤0.05) in gene expression for individual clones compared to Hs578T cells from blue (− 4, downregulation) to red (+ 4, upregulation). b Increased IL6 expression in HSP90i-resistant clones CR2 and CR3. Media from Hs578T, CR2 and CR3 cells after treatment with ganetespib (30 nM) for 24 h were subjected to the ELISA assay in order to measure the IL6 present in the media. The graph represents the mean IL6 concentration relative to DMSO-treated Hs578T cells from two independent experiments each performed in duplicate. Error bars indicate SEM. IL6 levels were significantly higher in CR2 and CR3 than Hs578T cells, where p values < 0.01 by two-way ANOVA with cell line and ganetespib treatment as factors. Ganetespib treatment did not significantly affect IL6 levels in Hs578T, CR2 or CR3 cells