The GR-LEDGF/p75-HSP27 Axis Contributes to Cross-Resistance Between Enzalutamide and Docetaxel in Prostate Cancer.
1/5 보강
An emerging challenge in prostate cancer (PCa) treatment is the development of drug cross-resistance, wherein resistance to enzalutamide (ENZ), an androgen receptor signaling inhibitor (ARSI), also co
- 표본수 (n) 4259
APA
Ochoa PT, Sanchez-Hernandez ES, et al. (2025). The GR-LEDGF/p75-HSP27 Axis Contributes to Cross-Resistance Between Enzalutamide and Docetaxel in Prostate Cancer.. Cells, 14(19). https://doi.org/10.3390/cells14191566
MLA
Ochoa PT, et al.. "The GR-LEDGF/p75-HSP27 Axis Contributes to Cross-Resistance Between Enzalutamide and Docetaxel in Prostate Cancer.." Cells, vol. 14, no. 19, 2025.
PMID
41090793 ↗
Abstract 한글 요약
An emerging challenge in prostate cancer (PCa) treatment is the development of drug cross-resistance, wherein resistance to enzalutamide (ENZ), an androgen receptor signaling inhibitor (ARSI), also confers resistance to subsequent ARSI and docetaxel (DTX) treatments. The mechanisms underlying this drug cross-resistance remain unclear. Through RNA sequencing, we identified 93 overlapping differentially expressed genes (DEGs) in ENZ- and DTX-resistant PCa cells. Among the DEGs, , which encodes heat shock protein 27 (HSP27), emerged as a key gene of interest. HSP27 is a known target of lens epithelium-derived growth factor p75 (LEDGF/p75), a transcription coactivator regulated by glucocorticoid receptor (GR). Both GR and LEDGF/p75 are overexpressed in advanced PCa and promote drug resistance. HSP27 was overexpressed in ENZ and DTX cross-resistant PCa cell lines and its expression was decreased upon GR or LEDGF/p75 silencing. ChIP sequencing confirmed GR binding at the promoter. Pharmacological targeting of HSP27 in drug-resistant cells reduced proliferation, clonogenicity, and tumorsphere formation, and restored sensitivity to ENZ and DTX. Notably, high transcript expression of a GR-LEDGF/p75-HSP27 gene panel correlated with worse overall survival in PCa patients (n = 4259). These findings identified this axis as a driver of PCa drug cross-resistance and promising therapeutic target for overcoming treatment failure.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Male
- Docetaxel
- Benzamides
- Drug Resistance
- Neoplasm
- Phenylthiohydantoin
- Prostatic Neoplasms
- HSP27 Heat-Shock Proteins
- Nitriles
- Cell Line
- Tumor
- Receptors
- Glucocorticoid
- Gene Expression Regulation
- Neoplastic
- Molecular Chaperones
- Animals
- Signal Transduction
- Adaptor Proteins
- Signal Transducing
- Mice
- Heat-Shock Proteins
- HSP27
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