ArticleNature communications2021
Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 162 citations in OpenAlex.
- Large-scale Genomic Landscape and Clinical Outcomes of De Novo and Treatment-emergent Neuroendocrine Prostate Cancer.European urology open science · 2026Article
- FOXA1 is a highly sensitive diagnostic marker for prostate cancer including small cell carcinoma of the prostate.Histopathology · 2026Article
- FOXA1 drives chemoresistance through activating Wnt pathway in small cell lung cancer.Translational lung cancer research · 2026Article
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- Review
- NKX2-1 regulates cell survival, maturation, and DNAdamage responses as a cofactor of RUNX1 in T-cell acute lymphoblastic leukemia.Haematologica · 2026Article
- c-Fos-driven metabolic switch of α-ketoglutarate orchestrates progression in prostate cancer.Cell death & disease · 2026Article
- 3D genome architecture and epigenetic regulation of lineage identity in advanced prostate cancer.Endocrinology · 2026Review
- 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
- Generation of a comprehensive epigenomic atlas in clear cell renal cell carcinoma informs kidney cancer progression and heritability.Cell reports · 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
- Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance.Journal of the National Cancer Center · 2026Review
- Identify the PANoptosis signature and prognostic model via a multimachine-learning computational framework for bladder urothelial carcinoma.Cancer cell international · 2026Article
- The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy.International journal of biological sciences · 2026Review
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Association of metabotropic glutamate receptor 7 gene with nicotine dependence in a Chinese Han population: A cross-sectional candidate-gene association study.Tobacco induced diseases · 2026Article
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
41 authors at 10 institutions in 3 countries.
Funding
Abstract
Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens. Here, we investigate the epigenomic basis of this resistance mechanism by profiling histone modifications in NEPC and PRAD patient-derived xenografts (PDXs) using chromatin immunoprecipitation and sequencing (ChIP-seq). We identify a vast network of cis-regulatory elements (N~15,000) that are recurrently activated in NEPC. The FOXA1 transcription factor (TF), which pioneers androgen receptor (AR) chromatin binding in the prostate epithelium, is reprogrammed to NE-specific regulatory elements in NEPC. Despite loss of dependence upon AR, NEPC maintains FOXA1 expression and requires FOXA1 for proliferation and expression of NE lineage-defining genes. Ectopic expression of the NE lineage TFs ASCL1 and NKX2-1 in PRAD cells reprograms FOXA1 to bind to NE regulatory elements and induces enhancer activity as evidenced by histone modifications at these sites. Our data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying cancer dependencies through epigenomic profiling.
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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.