ArticleScience advances2023
Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- CMV-GLA: contrastive multi-view graph layer attention for predicting phosphorylation site-disease associations.BMC bioinformatics · 2026Article
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- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- Pharmacological Inhibition of JNK Signalling Exerts Anti-Neoplastic Effects on SH-SY5Y Human Neuroblastoma Cells.International journal of molecular sciences · 2025Article
- Inclusion of JNK-independent drugs within multiagent chemotherapy improves response in relapsed high-risk neuroblastoma.Science advances · 2025Article
- The kinase ERK plays a conserved dominant role in the heterogeneity of epithelial-mesenchymal transition in pancreatic cancer cells.Science signaling · 2025Article
- Discovery of pyroptosis-inducing natural products in neuroblastomas: computational studies with experimental validation.BMC complementary medicine and therapies · 2025Article
- Stochastic gene expression in proliferating cells: Differing noise intensity in single-cell and population perspectives.PLoS computational biology · 2025Article
- The deubiquitinase USP44 enhances cisplatin chemosensitivity through stabilizing STUB1 to promote LRPPRC degradation in neuroblastoma.Neuro-oncology · 2025Article
- Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells.Cancer discovery · 2024Article
- Targeting therapy-persistent residual disease.Nature cancer · 2024Review
- Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network. Furthermore, we reveal that the memory of this initially random state is retained following chemotherapy treatment across a series of in vitro, in vivo, and patient models. Using matched PDX models established at diagnosis and relapse from individual patients, we show that HDAC inhibitor priming cannot erase the memory of this resistant state within relapsed neuroblastomas but improves response in the first-line setting by restoring drug-induced JNK activity within the chemoresistant population of treatment-naïve tumors.
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