FIGURE 1 from Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance

Elevated ATF5 expression correlates with poor outcomes in patients with neuroblastoma, and ATF5 silencing prolongs survival and inhibits metastatic progression in neuroblastoma-bearing mice. A, Violin plots of ATF5 expression in high-risk MYCN-amplified (MNA, red), high-risk MYCN-non-amplified (HR_NA, yellow), and low-risk stage 1 (LR_S1, green) patients. For SEQC, MNA = 92, HR_NA = 83, LR_S1 = 118. For TARGET, MNA = 68, HR_NA = 145, LR_S1 = 30. Expression data: SEQC (from GEO: GSE49711): https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49711; ref. 28); TARGET: HumanExon arrays (29). B, Kaplan–Meier curve depicting the corresponding increase in poor outcome with increasing ATF5 expression. The P value was calculated using a Cox proportional hazards model after removing stage 1 patient samples, Wald test, P = 1.57E-14. C, Bioluminescent images at day 10 and day 23 of mice bearing Dox-inducible BE(2)-C-shATF5-2 renal xenograft tumors and treated with or without Dox. D, Kaplan–Meier plot of mice bearing Dox-inducible BE(2)-C-shATF5-2 renal xenograft tumors with ATF5 knocked down (+ Dox, n = 10) or not (− Dox, n = 11). P = 0.0083, log-rank (Mantel–Cox). E,Ex vivo bioluminescent images of the liver at the time of euthanasia. F, Quantification of total flux (photons/second) by ex vivo liver bioluminescence at the time of euthanasia. G, Quantification of bone marrow metastases from bioluminescence of bone marrow homogenate (RLU/# BM cells) at the time of euthanasia. RLU: relative luciferase unit. H, Quantification of bioluminescence from blood representing the number of CTCs at the time of euthanasia. *, P < 0.05.