MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans
Abstract
The molecular roles of HOX transcriptional activity in human prostate epithelial cells remain unclear, impeding the implementation of new treatment strategies for cancer prevention and therapy. MEIS proteins are transcription factors that bind and direct HOX protein activity. MEIS proteins are putative tumor suppressors that are frequently silenced in aggressive forms of prostate cancer. Here we show that MEIS1 expression is sufficient to decrease proliferation and metastasis of prostate cancer cells in vitro and in vivo murine xenograft models. HOXB13 deletion demonstrates that the tumor-suppressive activity of MEIS1 is dependent on HOXB13. Integration of ChIP-seq and RNA-seq data revealed direct and HOXB13-dependent regulation of proteoglycans including decorin (DCN) as a mechanism of MEIS1-driven tumor suppression. These results define and underscore the importance of MEIS1-HOXB13 transcriptional regulation in suppressing prostate cancer progression and provide a mechanistic framework for the investigation of HOXB13 mutants and oncogenic cofactors when MEIS1/2 are silenced.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 18, 2020
- Source ID
- 10.7554/elife.53600
Entities
People
- Baizhen Zhu
- Calvin Vanopstall
- Donald J Vander Griend
- Hannah Brechka
- Marc Gillard
- Raj Bhanvadia
- Ryan Brown
- Sophia Lamperis
- Srikanth Perike
Organizations
- National Institutes of Health
- United States Department of Defense
- University of Chicago
- University of Illinois at Chicago
- University of Texas Southwestern Medical Center