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Record W4399457828 · doi:10.1038/s41467-024-49234-9

FOXA2 rewires AP-1 for transcriptional reprogramming and lineage plasticity in prostate cancer

2024· article· en· W4399457828 on OpenAlexafffund
Zifeng Wang, Scott L. Townley, Songqi Zhang, Mingyu Liu, Mu‐Qing Li, Maryam Labaf, Susan Patalano, Kavita Venkataramani, Kellee R. Siegfried, Jill A. Macoska, Dong Han, Shuai Gao, Gail P. Risbridger, Renea A. Taylor, Mitchell G. Lawrence, Housheng Hansen He, Luke A. Selth, Changmeng Cai

Bibliographic record

VenueNature Communications · 2024
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFOXO transcription factor regulation
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersCongressionally Directed Medical Research ProgramsCIHR Skin Research Training CentreNational Cancer InstituteCancer Council NSWCancer Council South AustraliaCanadian Institutes of Health ResearchMarshfield Clinic Research FoundationDepartment of Health, State Government of VictoriaNational Breast Cancer FoundationYuhanDepartment of Health and Human Services, State Government of VictoriaUniversity of Massachusetts BostonMovember FoundationGovernment of CanadaNational Institutes of HealthU.S. Department of Health and Human ServicesAustralian GovernmentU.S. Department of Defense
KeywordsReprogrammingLineage (genetic)Prostate cancerBiologyCancerProstateCancer researchGeneticsGene

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.917
Threshold uncertainty score0.357

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.021
GPT teacher head0.326
Teacher spread0.305 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations41
Published2024
Admission routes2
Has abstractyes

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