FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer.
| Title: | FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer. |
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| Authors: | Wang Z; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Yale Stem Cell Center, Department of Cell Biology and Department of Genetics, Yale University School of Medicine, New Haven, CT, 06510, USA.; Townley SL; Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, SA, 5042, Australia.; Freemasons Centre for Male Health and Wellbeing, Flinders University, Bedford Park, SA, 5042, Australia.; Zhang S; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Liu M; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Li M; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Labaf M; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Mathematics, University of Massachusetts Boston, Boston, MA, 02125, USA.; Patalano S; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Venkataramani K; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Siegfried KR; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Macoska JA; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Han D; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA.; Gao S; Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, 10595, USA.; Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, 10595, USA.; Risbridger GP; Melbourne Urological Research Alliance, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, VIC, 3800, Australia.; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, 3010, Australia.; Cabrini Institute, Cabrini Health, Malvern, VIC, 3144, Australia.; Taylor RA; Melbourne Urological Research Alliance, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, 3010, Australia.; Cabrini Institute, Cabrini Health, Malvern, VIC, 3144, Australia.; Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, VIC, 3800, Australia.; Lawrence MG; Melbourne Urological Research Alliance, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia.; Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, VIC, 3800, Australia.; Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.; Sir Peter MacCallum Department of Oncology, University of Melbourne, Victoria, 3010, Australia.; Cabrini Institute, Cabrini Health, Malvern, VIC, 3144, Australia.; He HH; Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G1L7, Canada.; Princess Margaret Cancer Center, University Health Network, Toronto, ON, M5G1L7, Canada.; Selth LA; Flinders University, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Bedford Park, SA, 5042, Australia.; Freemasons Centre for Male Health and Wellbeing, Flinders University, Bedford Park, SA, 5042, Australia.; Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, 5000, Australia.; Cai C; Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA. changmeng.cai@umb.edu.; Department of Biology, University of Massachusetts Boston, Boston, MA, 02125, USA. changmeng.cai@umb.edu. |
| Source: | Nature communications [Nat Commun] 2024 Jun 08; Vol. 15 (1), pp. 4914. Date of Electronic Publication: 2024 Jun 08. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : Nature Pub. Group |
| MeSH Terms: | Hepatocyte Nuclear Factor 3-beta*/metabolism ; Hepatocyte Nuclear Factor 3-beta*/genetics ; Prostatic Neoplasms*/genetics ; Prostatic Neoplasms*/metabolism ; Prostatic Neoplasms*/pathology ; Transcription Factor AP-1*/metabolism ; Transcription Factor AP-1*/genetics ; Cell Lineage* ; Gene Expression Regulation, Neoplastic*; Chromatin/metabolism ; Chromatin/genetics ; Enhancer Elements, Genetic/genetics ; Hepatocyte Nuclear Factor 3-alpha/metabolism ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Histone Demethylases/metabolism ; Histone Demethylases/genetics ; Proto-Oncogene Proteins c-jun/metabolism ; Proto-Oncogene Proteins c-jun/genetics ; Receptors, Androgen/metabolism ; Receptors, Androgen/genetics ; Animals ; Humans ; Male ; Mice ; Cell Line, Tumor ; Cell Plasticity ; Cellular Reprogramming ; Transcription, Genetic |
| 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.; (© 2024. The Author(s).) |
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| Grant Information: | R01 CA211350 United States CA NCI NIH HHS; W81XWH-21-1-0267 United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP); U54CA156734 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); MCRF15023 Department of Health, State Government of Victoria (Victorian Department of Health); 159567 Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre); MNBCF-17-012 Movember Foundation (Movember); W81XWH-19-1-0777 United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP); MCRF18017 Department of Health and Human Services, State Government of Victoria (Department of Health and Human Services); 142246 Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre); U54 CA156734 United States CA NCI NIH HHS; R01CA211350 U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI); W81XWH-19-1-0361 United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) |
| Substance Nomenclature: | 0 (Chromatin); 0 (FOXA1 protein, human); 0 (FOXA2 protein, human); 0 (Hepatocyte Nuclear Factor 3-alpha); 135845-92-0 (Hepatocyte Nuclear Factor 3-beta); EC 1.14.11.- (Histone Demethylases); EC 1.5.- (KDM1A protein, human); 0 (Proto-Oncogene Proteins c-jun); 0 (Receptors, Androgen); 0 (Transcription Factor AP-1) |
| Entry Date(s): | Date Created: 20240608 Date Completed: 20240608 Latest Revision: 20250306 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11162502 |
| DOI: | 10.1038/s41467-024-49234-9 |
| PMID: | 38851846 |
| Database: | MEDLINE |
Journal Article