Distinct transcription factor interactions drive HOXB13 activity in different stages of prostate cancer
Creators
- Ersoy-Fazlioglu, Betul
- Lingadahalli, Shreyas1
- Altintas, Umut Berkay1
- Cingoz, Ahmet
- Tekoglu, Emirhan
- Yu, Ivan Pak Lok1
- Dikbas, Meric1
- Missaghimamaghani, Olka1
- Yavuz, Kerim1
- Adomat, Hans1
- Kulac, Ibrahim2
- Morova, Tunc1
- Xiao, Kevin1
- Gleave, Martin
- Fazli, Ladan1
- Cejas, Paloma
- Cherkasov, Artem
- Zwart, Wilbert
- Haffner, Michael Christoph
- Long, Henry W.3
- 1. Vancouver Prostate Ctr, Vancouver, BC V6H 3Z6, Canada
- 2. Koc Univ, Sch Med, Dept Med Pharmacol, TR-34450 Istanbul, Turkiye
- 3. Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA
Description
HOXB13 is a lineage-specific transcription factor that plays a critical role in initiation and progression of prostate cancer (PCa). While most research has focused on the role of HOXB13 on androgen receptor (AR) activity, here we demonstrate that HOXB13 is frequently expressed in AR-negative tumors and is essential for the proliferation of both AR-positive and-negative PCa models. Strikingly, HOXB13 is remarkably selective and has almost no effect on nonprostatic tissues. Despite this common essentiality in PCa, HOXB13 activity is markedly different in AR-negative stem cell-like tumors, where interactions with the AP-1 change the HOXB13 cistrome and interactome. Yet despite these distinct activities, HOXB13 activity is commonly mediated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. The HOXB13/SMARCD2 interaction alters chromatin accessibility at HOXB13-binding sites, causing increased proliferation in AR-negative PCa. Overall, this work demonstrates a distinct mechanism of action for HOXB13 and highlights its critical role in AR-negative castration-resistant PCa.
Files
bib-4a813e1a-554b-4080-917c-f102f835f5cd.txt
Files
(472 Bytes)
| Name | Size | Download all |
|---|---|---|
|
md5:65b2bd7986208572b1fa66bcf2bf6bbd
|
472 Bytes | Preview Download |