SMARCA4 promotes lineage plasticity and enzalutamide resistance in prostate cancer by regulating PROX1 via H3K27 acetylation - PubMed
4 hours ago
- #SMARCA4
- #enzalutamide resistance
- #PROX1
- SMARCA4 is upregulated in enzalutamide-resistant prostate cancer cells and promotes resistance and lineage plasticity towards neuroendocrine prostate cancer (NEPC).
- Inhibition of SMARCA4 suppresses tumor progression and reverses neuroendocrine transformation in both in vitro and in vivo models.
- SMARCA4 regulates the transcription factor PROX1 by enhancing H3K27 acetylation and chromatin accessibility at the PROX1 locus.
- Targeting the SMARCA4-PROX1 axis is a potential therapeutic strategy to overcome enzalutamide resistance and NEPC progression.
- The tumor-suppressive effects of SMARCA4 knockdown can be reversed by histone deacetylase inhibitors (HDACi), similar to PROX1 overexpression.