Fig. 6: Polyamine depletion-mediated proteome rewiring induces neuroblastoma differentiation.
From: Reprogramming neuroblastoma by diet-enhanced polyamine depletion
a, GSEA across omics layers in all three treatment groups using the Hallmark gene set. Only the ProArg-free plus DFMO treatment group showed a significant effect compared with CD. The effect was mainly on the translation and protein level. Shown are the five top enriched sets (complete sets in Extended Data Fig. 10c). Size indicates P value (Benjamini–Hochberg correction) and colour represents NES, with red indicating enrichment in the intervention group (CD + DFMO, ProArg-free or ProArg-free + DFMO) and blue indicating enrichment in the CD group. b, Western blot analysis of MYCN in tumours from CD and ProArg-free plus DFMO treatment arms. Negative control (C1), CHLA20 neuroblastoma cell line (MYCN non-amplified, MYC expressing); positive control (C2), IMR5 neuroblastoma cell line (MYCN-amplified). GAPDH is used as a loading control. Blots are representative of two independent experiments yielding similar results. c, Representative haematoxylin and eosin (H&E)-stained sections. CD and ProArg-free diet treatments show undifferentiated primitive neuroblasts, absent neuropil and prominent mitotic figures. CD plus DFMO shows poorly differentiated primitive neuroblasts with scant neuropil (arrowhead) and foci of cytodifferentiation (<5% differentiating, arrow). ProArg-free diet plus DFMO tumours show high fractions of differentiating neuroblasts (>5% differentiating) with increased cytoplasmic to nuclear ratio (arrow) and abundant neuropil (arrowhead). Sections are representative of many images with the same observations. Scale bars, 50 μm. d, Summary of treatment effects. Cell cycle and MYCN programmes are downregulated at the protein level owing to translation inhibition and immature cancer cells are driven into neuronal differentiation. In a,c, RNA-seq: ProArg-free DFMO: n = 5; CD: n = 4. Ribo-seq: n = 5. Proteomics: ProArg-free DFMO: n = 6; CD: n = 5. Panel d created in BioRender. Morscher, R. (2025) https://BioRender.com/kk9n051.
