FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer
- Author(s)
- Wang, Z; Townley, SL; Zhang, S; Liu, M; Li, M; Labaf, M; Patalano, S; Venkataramani, K; Siegfried, KR; Macoska, JA; Han, D; Gao, S; Risbridger, GP; Taylor, RA; Lawrence, MG; He, HH; Selth, LA; Cai, C;
- Details
- Publication Year 2024-06-08,Volume 15,Issue #1,Page 4914
- Journal Title
- Nature Communications
- Publication Type
- Research article
- Abstract
- FOXA family proteins act as pioneer factors by remodeling compact chromatin structures. FOXA1 is crucial for the chromatin binding of the androgen receptor (AR) in both normal prostate epithelial cells and the luminal subtype of prostate cancer (PCa). Recent studies have highlighted the emergence of FOXA2 as an adaptive response to AR signaling inhibition treatments. However, the role of the FOXA1 to FOXA2 transition in regulating cancer lineage plasticity remains unclear. Our study demonstrates that FOXA2 binds to distinct classes of developmental enhancers in multiple AR-independent PCa subtypes, with its binding depending on LSD1. Moreover, we reveal that FOXA2 collaborates with JUN at chromatin and promotes transcriptional reprogramming of AP-1 in lineage-plastic cancer cells, thereby facilitating cell state transitions to multiple lineages. Overall, our findings underscore the pivotal role of FOXA2 as a pan-plasticity driver that rewires AP-1 to induce the differential transcriptional reprogramming necessary for cancer cell lineage plasticity.
- Publisher
- Springer Nature
- Keywords
- Male; Humans; *Hepatocyte Nuclear Factor 3-beta/metabolism/genetics; *Prostatic Neoplasms/genetics/metabolism/pathology; *Transcription Factor AP-1/metabolism/genetics; Cell Line, Tumor; *Gene Expression Regulation, Neoplastic; *Cell Lineage/genetics; Histone Demethylases/metabolism/genetics; Hepatocyte Nuclear Factor 3-alpha/metabolism/genetics; Receptors, Androgen/metabolism/genetics; Animals; Chromatin/metabolism/genetics; Cell Plasticity/genetics; Cellular Reprogramming/genetics; Mice; Proto-Oncogene Proteins c-jun/metabolism/genetics; Enhancer Elements, Genetic/genetics; Transcription, Genetic
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1038/s41467-024-49234-9
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-024-49234-9- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-27 07:14:42
Last Modified: 2024-08-27 07:28:18