Fig 2: Five year overall survival rates. (A) Cumulative overall survival five years after diagnosis related to CD271 expression profiles. CD271+ carcinomas showed significantly reduced overall survival rates compared to CD271− tumors. (B) Overall survival dependent on CD271/TrkC expression. CD271+/TrkC+ carcinomas showed higher survival rates compared to CD271+/TrkC−, however this difference was not significant (p = 0.128; log-rank test). (C–E) Survival rates dependent on Trk family member expression. (F) Overall survival dependent on CD271 expression and therapy. The best survival rate was demonstrated in CD271− carcinomas that received R(C)T. The worst survival rate was in CD271+ carcinomas that received R(C)T. This difference was significant.

Fig 3: Pathway and network analysis of regulated proteins and phosphosites. Significantly differentially abundant proteins (A) and p-sites (B) were annotated with and analyzed for enrichment of regulated Reactome pathways. Bubbles illustrate the hierarchical nature of biological pathways and respective sub-pathways; bubble sizes indicate numbers of proteins/p-sites annotated with the respective pathway; only LMNA-containing pathways are displayed. (C) STRING protein interaction network illustrating interactors of NTRK1/TrkA and their functional connection to LMNA.

Fig 4: Validation of inducible expression and activation of NTRK1 in four neuroblastoma cell lines. (A) NTRK1 expression was verified in the NTRK1-negative cell lines NGP, IMR5, SKNAS and SH-SY5Y using qPCR at time points indicated. (B) NTRK1 activation was validated for time points t = 1 h, 4 h and 24 h upon treatment with NGF using immunostaining of phosphorylated NTRK1 (pTrkA Y674/675). Numbers indicate the intensity ratio of the TrkA/pTrkA bands and Gapdh. Uncropped blots were added in supplemental materials.

Fig 5: The ATM/ATR DNA-damage signaling pathway is inhibited by TrkA/NTRK1 activation in SY5Y and Kelly cells. Representative Western blots showing expression and phosphorylation of TrkA/NTRK1, ATM, Chk1, and CDC25B. Expression of ß-Actin served as loading control. Original Western Blot data are provided as Supplementary Figure S8 (A) SY5Y and (B) Kelly TR and TRA cells. Cell were exposed to irradiation with 1 Gy and analyzed at time points thereafter as indicated.