Fig. 6.

The components of the TGF-β pathway targeted by the small molecule kartogenin are predictive of neuroblastoma patient outcome. a Schematic of the SMAD-RUNX portion of the TGF-β signalling pathway, showing how it is targeted by kartogenin (KGN). KGN inhibits FLNA, a negative regulator of the pathway, thereby activating SMAD-RUNX-dependent transcriptional regulation. This pathway is a modified version of the TGF-β pathway described in IPA. b Kaplan–Meier survival curves showing the predictive strength of the expression levels of the RUNX3, FLNA and CBFP mRNAs in neuroblastoma tumours on patient outcome. Plots generated using the Kocak [69] 649 neuroblastoma tumour dataset in the R2: Genomics Analysis and Visualization Platform (http://r2.amc.nl). c Activation/inhibition score of the SMAD ITRs which were altered in SY5Y-MYCN cells across the treatment groups. These values are generated, using IPA, from the SY5Y-MYCN RNA-seq data. Activation/inhibition values are relative to the corresponding SMAD activity levels of the SY5Y-MYCN control cells. d Kaplan–Meier survival curves showing the predictive strength of SMAD7 expression levels in neuroblastoma tumours on patient outcome. Plots generated as described for panel b