HOXB13 alters chromatin accessibility in prostate cancer through interactions with the SWI/SNF complex
Bibliographic record
Abstract
ABSTRACT HOXB13 is a posterior homeobox protein that is associated with the initiation and growth of prostate cancer (PCa). While most research has focused on the role of HOXB13 on androgen receptor (AR) activity, we demonstrate that HOXB13 is essential to the proliferation of both AR-positive and -negative PCa. Strikingly, HOXB13 is remarkably selective and has almost no effect on non-prostatic tissues. Despite this common essentiality in PCa, HOXB13 activity is markedly different in AR-negative PCa, where interactions with the AP-1 change the HOXB13 cistrome in stem-cell like castration-resistant prostate cancer. We show that HOXB13 activity is commonly mediated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. Despite the distinct transcription factor interactions in AR-positive and -negative PCa the HOXB13/SMARCD2 commonly alters chromatin accessibility at HOXB13 binding sites that causes increased proliferation in PCa. Overall, this work demonstrates a novel mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant prostate cancer.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".