ArticleNature cancer2025
CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors.
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- ATP-dependent chromatin remodelers in prostate cancer progression and therapeutic resistance.Endocrinology · 2026Review
- SARIFA and Lipid Metabolic Reprogramming in Prostate Cancer: Fundamental Mechanisms, Tumor Microenvironment, and Novel Biomarker Prospects.Life (Basel, Switzerland) · 2026Review
- Design, synthesis, and anti-prostate cancer activity evaluation of novel thieno[2,3-b]pyridine derivatives as potential BLM helicase inhibitors.Molecular diversity · 2026Article
- Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis.Nature communications · 2026Article
- Protocol for genomic mapping of chromatin targets using high-throughput CUT&RUN.STAR protocols · 2026Article
- Development of High-Affinity CHD1 Chromodomain Inhibitors.Journal of medicinal chemistry · 2026Article
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Game of clones: decipher lineage plasticity in hormone-driven cancers.Cellular and molecular life sciences : CMLS · 2026Review
- SENP1 drives de novo cholesterogenesis via disrupting SUMOylation-mediated SREBP2-FBXW7 interaction.Cancer & metabolism · 2026Article
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Review
- NUDT21-mediated Alternative Polyadenylation of CDK19 Reprograms Cholesterol Biosynthesis to Drive Colorectal Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance.Frontiers in immunology · 2026Review
- Intratumoral Androgens and Genetic Variants Driving Therapy Resistance in Prostate Cancer.Research (Washington, D.C.) · 2026Review
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- CHD1 status drives divergent metabolic pathways in SPOP-mutant prostate cancer.Nature cancer · 2025Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Despite undergoing castration, most individuals with prostate cancer (PCa) experience progression to castration-resistant PCa (CRPC), in which the androgen receptor (AR) remains an important driver. Concurrent genetic alterations in SPOP and CHD1 define a unique subtype of PCa, but their interactions in tumor progression and therapy response remain unclear. Here, we provide genetic evidence supporting that CHD1 loss accelerates disease progression and confers resistance to castration in males with SPOP-mutated PCa. By leveraging genetic engineering and multiomics, we uncovered a noncanonical function of CHD1 in lipid metabolism reprogramming via repressing the SREBP2 transcriptome. Loss of CHD1 induces cholesterol production, supplies intratumoral androgen biosynthesis and enhances AR activity, leading to castration resistance of SPOP-mutated PCa. Combining anti-androgen therapy with cholesterol-lowering drugs showed synergistic and durable activity against CRPC harboring CHD1 loss and SPOP mutations. These findings advance our understanding of an emerging PCa subtype and offer biomarker-driven combinatorial treatment strategies for men with CRPC.
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