Fig. 4
DNA methylation profiles that drive EMT are shared and confer cross-resistance. a The number of CpGs differentially methylated between resistant and parental cell lines, that are shared between pairs of resistant cell lines. Shown are the number of shared hyper- (red) and hypo- (blue) methylated CpGs for each resistant cell line pair (x-axis; log10 scale), versus the associated p values (y-axis; -log10 scale) of binomial tests assessing whether the number of shared hyper- or hypomethylated CpGs is significantly higher than expected. The horizontal dotted line indicates p value = 0.05. Primary data are shown in (Additional file 1: Tables S2, S3 and S4). b Cross-resistance of the resistant cell lines to various other therapies. Shown is the difference in growth between resistant and parental cells after exposure to the drugs indicated in the legend. Positive values indicate that resistant cells have a growth advantage upon drug exposure compared to their parental counterparts. Drug concentrations are as per (Additional file 1: Table S5). Cell growth was normalized to resistant and parental cells unexposed to drugs. Arrows indicate the drug to which the cells originally acquired resistance. Shown are individual data points and means of experiments that were performed in triplicate, each replication consisting of nine technical replicates. c Loss of cross-resistance after demethylation. As in panel (b), but for growth inhibition (as defined in ‘Methods’) of parental—resistant cells demethylated through an 8-day treatment with 0.5 μM 5-aza-2′-deoxycytidine. Negative values indicate resistant cell growth under drug pressure is more hindered after demethylation compared to their parental counterparts