RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon
Abstract
Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, that identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes in their target regulons. Application of this approach to data collected from clinical samples, patient-derived xenografts, and cell line models of colon cancer metastasis revealed the RNA-binding protein RBMS1 as a suppressor of colon cancer progression. We observed that silencing RBMS1 results in increased metastatic capacity in xenograft mouse models, and that restoring its expression blunts metastatic liver colonization. We have found that RBMS1 functions as a posttranscriptional regulator of RNA stability by directly binding its target mRNAs. Together, our findings establish a role for RBMS1 as a previously unknown regulator of RNA stability and as a suppressor of colon cancer metastasis with clinical utility for risk stratification of patients.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2020
- Source ID
- 10.1158/2159-8290.cd-19-1375
Entities
People
- Albertas Navickas
- Benjamin Hänisch
- Bruce Culbertson
- Ethan M. Weinberg
- Faraz Khosravi Mardakheh
- Hani Goodarzi
- Hosseinali Asgharian
- John Paolo Olegario
- Johnny Yu
- Kristle Garcia
- Lisa Fish
- Maria Dermit
- Martin Dodel
- Robert S Warren
- Rodrigo Dienstmann
- Yikai Luo
Organizations
- American Association for Cancer Research
- Medical Research Council
- National Institutes of Health
- Queen Mary University of London
- United States Department of Defense
- University of California, San Francisco
- University of Pennsylvania