MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans
- The University of Chicago, United States
- The University of Illinois at Chicago, United States
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.
Data availability
RNA-seq and ChIP-seq raw and analyzed data have been deposited at the Gene Expression Omnibus and Sequence Read Archive under the accession number GSE132717.
Article and author information
Author details
Donald J Vander Griend
Funding
U.S. Department of Defense (PC130587)
- Donald J Vander Griend
U.S. Department of Defense (PC180414)
- Donald J Vander Griend
National Institutes of Health (P50 CA180995)
- Donald J Vander Griend
National Institutes of Health (T32 CA009594)
- Calvin VanOpstall
- Hannah Brechka
- Donald J Vander Griend
National Institutes of Health (F31CA232651)
- Calvin VanOpstall
National Institutes of Health (P30CA014599)
- Donald J Vander Griend
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the University of Chicago Institutional Animal Care and Use Committee (IACUC) (protocol #72231) as well as by the University of Illinois at Chicago IACUC (protocol #18-100).
Reviewing Editor
- Wilbert Zwart, Netherlands Cancer Institute, Netherlands
Publication history
- Received: November 14, 2019
- Accepted: June 17, 2020
- Accepted Manuscript published: June 18, 2020 (version 1)
- Version of Record published: July 20, 2020 (version 2)
Copyright
© 2020, VanOpstall et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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MEIS-mediated suppression of human prostate cancer growth and metastasis through HOXB13-dependent regulation of proteoglycans
eLife 9:e53600.
https://doi.org/10.7554/eLife.53600
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