Cited by Steroid receptor-assisted loading modulates transcriptional responses in prostate cancer cells

Steroid receptor-assisted loading modulates transcriptional responses in prostate cancer cells DOI

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

ABSTRACT Steroid receptors are involved in a wide array of crosstalk mechanisms that regulate diverse biological processes, with significant implications diseases, particularly cancers. In prostate cancer, indirect between androgen receptor (AR) and glucocorticoid (GR) is well-documented, where GR replaces antiandrogen-inactivated AR becoming the disease driver. However, existence impact direct chromatin cancer have remained elusive. Our genome-wide investigations reveal activation significantly expands binding. Mechanistically, induces remodeling closed sites, facilitating binding to inaccessible sites. Importantly, coactivation results distinct transcriptional responses at both cell population single-cell levels. Intriguingly, pathways affected by these changes generally associated improved patient survival. Thus, yields markedly different outcomes from known role circumventing blockade antiandrogens.

Language: Английский

Regulation of glucocorticoid receptor nuclear localization in prostate cancer cells DOI

Guang Chen, Shidong Lv, Laura E. Pascal

et al.

Journal of Pharmacology and Experimental Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 103577 - 103577

Published: April 1, 2025

Glucocorticoid receptor (GR) plays important roles in many diseases including prostate cancer. Intracellular shuttling of GR is thought to be an mechanism regulating its localization the nucleus required for transactivation target genes. Here, using fluorescent microscopy coupled with pulse-chase and nucleocytoplasmic fractionation western blot, we provided evidence that can imported then degraded absence ligand. We also showed nuclear was stabilized by glucocorticoid hormone withdrawal caused degradation, but not export. Further analysis ubiquitination occurred predominantly compared cytoplasm suppressed glucocorticoids. Using small interfering RNA knockdown, loss E3 ligase CHIP significantly inhibited degradation nucleus, while enhancing expression gene SGK1. These findings support updated model trafficking a 1-way trip, involving import Future studies should focus on defining mechanisms which may lead novel approaches modulate function disease treatment. SIGNIFICANCE STATEMENT: This study suggests will guide future localization,

Language: Английский

Citations

Urolithins: Emerging natural compound targeting castration-resistant prostate cancer (CRPC) DOI