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CHD1 Loss Hijacks SREBP2-mediated Cholesterol Biosynthesis to Fuel SPOP-deficient Prostate Cancer and Confers Resistance to Castration [scRNA-seq]

GSE273102 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2025/02/10 Platform GPL24247
Summary
Androgen receptor (AR) is an important driver in the disease progression of castration-resistant prostate cancer (CRPC). Speckle-type BTB/POZ protein (SPOP) mutations stabilize AR and frequently co-occur with the loss of chromodomain helicase DNA-binding protein 1 (CHD1). We generated a new genetically engineered mouse model and prostate cancer cells model containing CHD1 deletion and SPOP mutation to study the underlying mechanism. We found CHD1 loss–induced cholesterol production supplies intratumoral androgen biosynthesis and retains AR transcriptional activity in SPOP-mutated prostate tumors, leading to castration resistance.
Published in
CHD1 loss reprograms SREBP2-driven cholesterol synthesis to fuel androgen-responsive growth and castration resistance in SPOP-mutated prostate tumors
Chen F, Li H, Wang Y et al. · Nature cancer 2025 · PMID 40360905 · doi:10.1038/s43018-025-00952-z
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Also filed as BioProject PRJNA1140183 and SRA study SRP522206. Searching any of these in the dataset finder brings you back here.

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