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Transformation of the intestinal epithelium by the MSI2 RNA binding protein
The MSI2 RNA binding protein is a potent oncogene playing key roles in hematopoietic stem cell homeostasis and malignant hematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 los...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643281/ https://www.ncbi.nlm.nih.gov/pubmed/25774828 http://dx.doi.org/10.1038/ncomms7517 |
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author | Wang, Shan Li, Ning Yousefi, Maryam Nakauka-Ddamba, Angela Li, Fan Parada, Kimberly Rao, Shilpa Minuesa, Gerard Katz, Yarden Gregory, Brian D. Kharas, Michael G. Yu, Zhengquan Lengner, Christopher J. |
author_facet | Wang, Shan Li, Ning Yousefi, Maryam Nakauka-Ddamba, Angela Li, Fan Parada, Kimberly Rao, Shilpa Minuesa, Gerard Katz, Yarden Gregory, Brian D. Kharas, Michael G. Yu, Zhengquan Lengner, Christopher J. |
author_sort | Wang, Shan |
collection | PubMed |
description | The MSI2 RNA binding protein is a potent oncogene playing key roles in hematopoietic stem cell homeostasis and malignant hematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss of function abrogates colorectal cancer cell growth. MSI2 gain of function in the intestinal epithelium in a drug inducible mouse model is sufficient to phenocopy many of the morphological and molecular consequences of acute loss of the APC tumor suppressor in the intestinal epithelium in a Wnt-independent manner. Transcriptome-wide RNA-binding analysis indicates that MSI2 acts as a pleiotropic inhibitor of known intestinal tumor suppressors including Lrig1, Bmpr1a, Cdkn1a, and Pten. Finally, we demonstrate that inhibition of the PDK-AKT-mTORC1 axis rescues oncogenic consequences of MSI2 induction. Taken together, our findings identify MSI2 as a central component in an unappreciated oncogenic pathway promoting intestinal transformation. |
format | Online Article Text |
id | pubmed-4643281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-46432812015-11-13 Transformation of the intestinal epithelium by the MSI2 RNA binding protein Wang, Shan Li, Ning Yousefi, Maryam Nakauka-Ddamba, Angela Li, Fan Parada, Kimberly Rao, Shilpa Minuesa, Gerard Katz, Yarden Gregory, Brian D. Kharas, Michael G. Yu, Zhengquan Lengner, Christopher J. Nat Commun Article The MSI2 RNA binding protein is a potent oncogene playing key roles in hematopoietic stem cell homeostasis and malignant hematopoiesis. Here we demonstrate that MSI2 is expressed in the intestinal stem cell compartment, that its expression is elevated in colorectal adenocarcinomas, and that MSI2 loss of function abrogates colorectal cancer cell growth. MSI2 gain of function in the intestinal epithelium in a drug inducible mouse model is sufficient to phenocopy many of the morphological and molecular consequences of acute loss of the APC tumor suppressor in the intestinal epithelium in a Wnt-independent manner. Transcriptome-wide RNA-binding analysis indicates that MSI2 acts as a pleiotropic inhibitor of known intestinal tumor suppressors including Lrig1, Bmpr1a, Cdkn1a, and Pten. Finally, we demonstrate that inhibition of the PDK-AKT-mTORC1 axis rescues oncogenic consequences of MSI2 induction. Taken together, our findings identify MSI2 as a central component in an unappreciated oncogenic pathway promoting intestinal transformation. 2015-03-16 /pmc/articles/PMC4643281/ /pubmed/25774828 http://dx.doi.org/10.1038/ncomms7517 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wang, Shan Li, Ning Yousefi, Maryam Nakauka-Ddamba, Angela Li, Fan Parada, Kimberly Rao, Shilpa Minuesa, Gerard Katz, Yarden Gregory, Brian D. Kharas, Michael G. Yu, Zhengquan Lengner, Christopher J. Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title | Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title_full | Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title_fullStr | Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title_full_unstemmed | Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title_short | Transformation of the intestinal epithelium by the MSI2 RNA binding protein |
title_sort | transformation of the intestinal epithelium by the msi2 rna binding protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643281/ https://www.ncbi.nlm.nih.gov/pubmed/25774828 http://dx.doi.org/10.1038/ncomms7517 |
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