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Direct ERG-to-glucocorticoid receptor interactions enhance tumorigenicity and might explain the enigmatic responses of prostate cancers to corticosteroids (RNA-Seq)

GSE247422 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/11/01 Platform GPL24676
Summary
Patients with prostate cancer (PCa) frequently express fusions between an androgen-regulated gene and anETSfamily gene, especiallyERG. Our protein complementation assays revealed that the glucocorticoid receptor, GR, physically interacts with ERG. This alleviates allosteric autoinhibition, stabilizes ERG and protects it from chemotherapy-induced degradation. Promoter-reporter assays indicated that GR transactivates ERG’s target genes, includingMYC. In PCa models, antagonizing GR or lowering cortisol increased apoptosis and decreased tumorigenic growth of ERG-positive, not ERG-negative PCa cells. Likewise, ERG+patient-derivedxenografts displayedintensifiedsensitivity tothe combination of aGRantagonist and an inhibitor of the androgen receptor (AR). In summary, we uncovered an oncogenic partner of ERG, identified a potential molecular basis for the association of corticosteroid use with poor responses to AR signaling inhibitors, as well as offer new strategies to treat a sizable group of patients with PCa.
Published in
TMPRSS2-ERG confers resistance of prostate cancer to antiandrogens
Sekar A, Selvadurai BR, Chatterjee R et al. · EMBO molecular medicine 2026 · PMID 42120493 · doi:10.1038/s44321-026-00423-7
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Also filed as BioProject PRJNA1037533 and SRA study SRP471465. Searching any of these in the dataset finder brings you back here.

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