Many congratulations to the lead authors Betul Ersoy-Fazlioglu and Shreyas Lingadahalli. I'd also like to thank the numerous collaborators including Tugba Bagci-Onder, Colin Collins, Henry Long, Michael Haffner, Wilbert Zwart, Artem Cherkasov, Paloma Cejas, Ladan Fazli, Martin Gleave and others.

Why this matters: HOXB13 is a context-adaptive lineage TF. As prostate cancer progresses, HOXB13 rewires its partners while preserving a common output. This provides a explanation for AR-independent growth in CRPC and highlights HOXB13–SMARCD2 as a potential therapeutic vulnerability.
(6/6)

Even though HOXB13 switches transcription factor partners, its downstream effector stays the same. In both contexts, HOXB13 engages the mSWI/SNF complex. This interaction increases chromatin accessibility and is required for HOXB13-driven prostate cancer growth.
(5/6)

HOXB13’s protein partners change with stage:
• In AR⁺ PCa, HOXB13 integrates into the AR transcriptional complex
• In AR⁻ stem-like CRPC, HOXB13 instead engages the AP-1 complex (JUN/FOS)

Distinct interactomes mirror the rewired cistromes and shows that HOXB13 is context-specific, not static.
(4/6)

While both disease stage depend on the same TF, HOXB13 activity is totally changed:
• AR⁺ PCa → AR / FOXA1 / GATA2
• AR⁻ stem-like CRPC → AP-1 (JUN/FOS)

Same protein. Different binding sites (<10% overlap) (3/6)

We show that HOXB13 is essential for growth in
• AR⁺ prostate cancer
• AR⁻ stem-like CRPC

Yet it has minimal effects outside the prostate.
That’s rare and therapeutically interesting.
(2/6)

Many congratulations 🎉🎉🎉🎉