Neuroblastoma signalling models unveil combination therapies targeting feedback-mediated resistance
Fig 5
Phosphoproteomics analysis reveals important variations in the response to combination treatment.
A-B: Venn diagrams showing the overlap in differentially regulated phosphosites A: between IMR32 and N206 or B: between treatments for each cell line. C: Phosphopeptides synergistically altered by MEKi+IGFRi combination (black outline) when compared to the sum of individual inhibitor treatments. AKT, mTOR or P70S6K bona fide targets (bold font) and putative targets (italic font; top 5 predicted kinases by PhosphoNET Kinase Predictor www.phosphonet.ca) are indicated. D: Kinase substrate enrichment score using PhosphoSitePlus annotations. E: Log-fold change to DMSO for RAF/MAPK and MYCN phosphopeptides. C-E: Black outline highlights significant changes in activity (limma moderated t-test, FDR<5%) F-H: Relative levels compared to control of the total proteins levels for MYCN (F) and CCND1 (H) measured with mass spectrometry and MYCN measured with Western blot (G).