RBMS1 Suppresses Colon Cancer Metastasis through Targeted Stabilization of Its mRNA Regulon.

Cancer Discovery
J. YuHani Goodarzi

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. SIGNIFICANCE: By applying a new analytic approach to transcriptomic data from clinical samples and models of colon cancer progression, we have identified RBMS1 as a suppressor of metastasis and as a post-transcrip...Continue Reading

References

Oct 17, 2003·Oncogene·Martin JechlingerNorbert Kraut
May 25, 2004·International Journal of Experimental Pathology·Mona El-BahrawyIan T Tomlinson
Mar 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maguy Del RioMarc Ychou
Oct 30, 2007·Molecular Cell·Olivier ElementoSaeed Tavazoie
Mar 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wilko WeichertCarsten Denkert
May 17, 2008·Cancer Research·Tamer T OnderRobert A Weinberg
Jun 27, 2008·Cellular and Molecular Life Sciences : CMLS·M N Hinman, H Lou
Apr 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Michal ShefferEytan Domany
Jun 19, 2009·Advances in Enzyme Regulation·Danuta WawrzakPascale Zimmermann
Dec 17, 2009·Molecular Cell·Hani GoodarziSaeed Tavazoie
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Joseph H TaubeSendurai A Mani
Jul 5, 2011·Molecular Cell·Svetlana LebedevaNikolaus Rajewsky
Jul 13, 2013·Nature·Debashish RayTimothy R Hughes
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 21, 2015·Cell·Jia Min LooSohail F Tavazoie
Jul 28, 2015·Nature Biotechnology·Babak AlipanahiBrendan J Frey
Apr 26, 2016·Nature Methods·Brian J ZarnegarPaul A Khavari
Sep 8, 2016·Cold Spring Harbor Perspectives in Medicine·Yixuan Li, Edward Seto
Apr 18, 2017·Current Colorectal Cancer Reports·Emma M SchatoffLukas E Dow
Aug 8, 2017·Nature·Dan R RobinsonArul M Chinnaiyan
Dec 21, 2017·Cancers·Trung Vu, Pran K Datta
Jan 10, 2018·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 31, 2019·Nucleic Acids Research·Harry FischlAndre Furger
Jan 24, 2020·Wiley Interdisciplinary Reviews. RNA·Christopher W SchultzJonathan R Brody

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Citations

Oct 6, 2021·The Journal of Clinical Investigation·Wenjing ZhangYang Wang
Nov 23, 2021·Frontiers in Oncology·Zhigang LiJing Tang

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