ArticleThe Journal of clinical investigation2019
N-Myc-mediated epigenetic reprogramming drives lineage plasticity in advanced prostate cancer.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed, 189 citations in OpenAlex.
- Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer.The Journal of clinical investigation · 2020Trial
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- The Great Escape: the systems biology of endocrine resistance and lineage plasticity.Endocrine-related cancer · 2026Review
- Clinical and genomic predictors of sipuleucel-T outcomes in men with metastatic androgen pathway modulator resistant prostate cancer.Research square · 2026Article
- Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs).Gene · 2026Review
- Single-Cell Analysis Reveals Pre-Existing Basal-Associated Epithelial States in Metastatic Hormone-Naïve Prostate Cancer.International journal of molecular sciences · 2026Article
- Review
- c-Fos-driven metabolic switch of α-ketoglutarate orchestrates progression in prostate cancer.Cell death & disease · 2026Article
- Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): trial protocols.Future oncology (London, England) · 2026Article
- Targeting Wnt/β-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell state diversity.The Journal of clinical investigation · 2026Article
- Game of clones: decipher lineage plasticity in hormone-driven cancers.Cellular and molecular life sciences : CMLS · 2026Review
- Review
- Deciphering double-negative prostate cancer: from aggressive subtype to novel therapeutic paradigms.Cell communication and signaling : CCS · 2026Review
- Integrated single-cell and spatial transcriptomic profiling decodes lineage plasticity and immune microenvironment remodeling in prostate cancer progression.Molecular cancer · 2026Article
- Crosstalk between EZH2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity.Nature communications · 2026Article
- ERRγ impedes neuroendocrine prostate cancer development.Genes & development · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Mechanisms and implications of epithelial cell plasticity in the bladder.Nature reviews. Urology · 2026Review
- KDM4A promotes NEPC progression through regulation of MYC expression.Cancer letters · 2026Article
77 more citing papers are in PubMed but not listed here.
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20 authors at 3 institutions in 4 countries.
Funding
Abstract
Despite recent therapeutic advances, prostate cancer remains a leading cause of cancer-related death. A subset of castration resistant prostate cancers become androgen receptor (AR) signaling-independent and develop neuroendocrine prostate cancer (NEPC) features through lineage plasticity. These NEPC tumors, associated with aggressive disease and poor prognosis, are driven, in part, by aberrant expression of N-Myc, through mechanisms that remain unclear. Integrative analysis of the N-Myc transcriptome, cistrome and interactome using in vivo, in vitro and ex vivo models (including patient-derived organoids) identified a lineage switch towards a neural identity associated with epigenetic reprogramming. N-Myc and known AR-co-factors (e.g., FOXA1 and HOXB13) overlapped, independently of AR, at genomic loci implicated in neural lineage specification. Moreover, histone marks specifically associated with lineage-defining genes were reprogrammed by N-Myc. We also demonstrated that the N-Myc-induced molecular program accurately classifies our cohort of patients with advanced prostate cancer. Finally, we revealed the potential for EZH2 inhibition to reverse the N-Myc-induced suppression of epithelial lineage genes. Altogether, our data provide insights on how N-Myc regulates lineage plasticity and epigenetic reprogramming associated with lineage-specification. The N-Myc signature we defined could also help predict the evolution of prostate cancer and thus better guide the choice of future therapeutic strategies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.