Fig. 3: Lysosomal adaptation to drug treatment.

A Quantification of lysosome count per cell based on immunofluorescent co-staining of YAP1 and LAMP1 in mixed cell line SK-N-SH treated with etoposide, doxorubicin and irinotecan. Number of lysosomes per cell in YAP1 staining positive and negative cells. Gray dots represent the number of individual cells. B Heatmap of lysosomal adaptation score of 8 neuroblastoma cell lines to 84 drugs, with genetic information of the cell lines in the top annotation. C PCA analysis was performed on the lysosomal adaptation score of 8 neuroblastoma cell lines. Dots represent cell lines and are colored according to the mesenchymal-adrenergic gene signature score. D Number of lysosomal foci per nucleus after 72 h of chemotherapy treatment with irinotecan, etoposide and doxorubicin for increasing concentrations in mesenchymal SH-EP and adrenergic IMR-5/75 cell line. E Number of lysosomal foci normalized to DMSO treatment for the treatment of SH-EP (left) and IMR-5/75 (right) cells with six inhibitors of the MAPK pathway. Five MEKi (trametinib, selumetinib, cobimetinib, binimetinib, pimasertib) and one ERKi (ulixertinib) were tested. Kruskal–Wallis test with post hoc Dunn comparison, non-significant comparisons not displayed, *** = padj < 0.001, ** padj < 0.01, * = padj < 0.05.