HOXB13-Dependent Metastasis Suppression of Prostate Cancer by Proteoglycan Signaling
Abstract
HOXB13 is the predominant HOX gene expressed in prostate epithelial cells, and germline mutations in HOXB13 are strongly associated with increased prostate cancer incidence. Significant research has focused on the role of HOXB13 as it relates to Androgen Receptor (AR)signaling and cancer cell responses to AR-targeted therapies. Our laboratory recently determined that the HOX co-factors MEIS1 andMEIS2 are novel tumor suppressor genes in prostate cancer, are the predominant HOXB13 binding partner in non-malignant prostate epithelial cells, and interfere with oncogenic AR/HOXB13 transcription. MEIS proteins function as critical transcriptional co-factors during development and within adult tissues to bind HOX proteins and specify HOX gene targeting. In fact, the majority of germline HOXB13mutations are located within the MEIS-interacting domain, emphasizing the importance of MEIS/HOX interactions in prostate tumor biology.Our data supports a critical tumor-suppressive and anti-androgen role for MEIS proteins in prostate cancer, and while HOXB13 mutations are uncommon, we have shown that MEIS proteins are frequently down-regulated in prostate tumors. However, there remain significant gaps in our understanding of the mechanistic function of MEIS proteins to block metastatic progression, and the impact of HOXB13mutations on MEIS binding and gene regulation; filling such knowledge gaps has a high potential to functionally implicate new biomarkers to predict cancer progression and new targets to therapeutically block prostate cancer metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1196240
Entities
People
- Donald J Vander Griend
Organizations
- University of Illinois at Chicago