Distinct transcription factor interactions drive HOXB13 activity in different stages of prostate cancer [ATAC-seq ]

Homeobox-B13 (HOXB13) is a master transcriptional regulator which is exclusively expressed in the prostate tissue and has been shown to be crucial for its embryonic development. There is extensive clinical and experimental evidence to support the role of HOXB13 in prostate cancer (PCa). Yet, despite this critical role, the function of HOXB13 remains controversial with some studies supporting an oncogenic role and others demonstrating a tumor-suppressive role. While there is a clear relationship between HOXB13 and AR there are conflicting studies if HOXB13 is itself regulated by AR. Interrogating various AR +ve and AR -ve in-vivo and in-vitro models, in this study, we demonstrate that HOXB13 is crucial for the growth and proliferation of PCa regardless of its androgen dependency. We show that HOXB13 activity in these different models is mediated via interactions with cell-specific transcription factors. Yet despite the diverse transcription factor interactions, HOXB13 activity is commonly modulated by SMARCD2, a member of the mSWI/SNF chromatin remodeling complex. The HOXB13/SMARCD2 interaction is stabilized through interactions with transcription factors. This interaction alters the chromatin accessibility at HOXB13 binding sites which leads to increased proliferation in PCa.