The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins
Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715013224 |
| _version_ | 1819275299324428288 |
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| author | Ning Li Maryam Yousefi Angela Nakauka-Ddamba Fan Li Lee Vandivier Kimberly Parada Dong-Hun Woo Shan Wang Ammar S. Naqvi Shilpa Rao John Tobias Ryan J. Cedeno Gerard Minuesa Katz Y Trevor S. Barlowe Alexander Valvezan Sheila Shankar Raquel P. Deering Peter S. Klein Shane T. Jensen Michael G. Kharas Brian D. Gregory Zhengquan Yu Christopher J. Lengner |
| author_facet | Ning Li Maryam Yousefi Angela Nakauka-Ddamba Fan Li Lee Vandivier Kimberly Parada Dong-Hun Woo Shan Wang Ammar S. Naqvi Shilpa Rao John Tobias Ryan J. Cedeno Gerard Minuesa Katz Y Trevor S. Barlowe Alexander Valvezan Sheila Shankar Raquel P. Deering Peter S. Klein Shane T. Jensen Michael G. Kharas Brian D. Gregory Zhengquan Yu Christopher J. Lengner |
| author_sort | Ning Li |
| collection | DOAJ |
| description | Members of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers. |
| first_indexed | 2024-12-23T23:22:07Z |
| format | Article |
| id | doaj.art-48f8b5528eca4e5fa6bb5060ea98df07 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T23:22:07Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-48f8b5528eca4e5fa6bb5060ea98df072022-12-21T17:26:18ZengElsevierCell Reports2211-12472015-12-0113112440245510.1016/j.celrep.2015.11.022The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal OncoproteinsNing Li0Maryam Yousefi1Angela Nakauka-Ddamba2Fan Li3Lee Vandivier4Kimberly Parada5Dong-Hun Woo6Shan Wang7Ammar S. Naqvi8Shilpa Rao9John Tobias10Ryan J. Cedeno11Gerard Minuesa12Katz Y13Trevor S. Barlowe14Alexander Valvezan15Sheila Shankar16Raquel P. Deering17Peter S. Klein18Shane T. Jensen19Michael G. Kharas20Brian D. Gregory21Zhengquan Yu22Christopher J. Lengner23State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100194, ChinaCell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAState Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100194, ChinaDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USAPENN Molecular Profiling Facility, University of Pennsylvania, Philadelphia, PA 19104, USAPENN Molecular Profiling Facility, University of Pennsylvania, Philadelphia, PA 19104, USACell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USAMolecular Pharmacology and Chemistry Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USABroad Institute of Harvard and MIT, Cambridge, MA 02142, USAMolecular Pharmacology and Chemistry Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USACell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USABroad Institute of Harvard and MIT, Cambridge, MA 02142, USACell and Molecular Biology Graduate Program, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104, USAMolecular Pharmacology and Chemistry Program, Experimental Therapeutics Center and Center for Stem Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USADepartment of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USAState Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100194, ChinaCenter for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia, PA 19104, USAMembers of the Msi family of RNA-binding proteins have recently emerged as potent oncoproteins in a range of malignancies. MSI2 is highly expressed in hematopoietic cancers, where it is required for disease maintenance. In contrast to the hematopoietic system, colorectal cancers can express both Msi family members, MSI1 and MSI2. Here, we demonstrate that, in the intestinal epithelium, Msi1 and Msi2 have analogous oncogenic effects. Further, comparison of Msi1/2-induced gene expression programs and transcriptome-wide analyses of Msi1/2-RNA-binding targets reveal significant functional overlap, including induction of the PDK-Akt-mTORC1 axis. Ultimately, we demonstrate that concomitant loss of function of both MSI family members is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. Our findings demonstrate that MSI1 and MSI2 act as functionally redundant oncoproteins required for the ontogeny of intestinal cancers.http://www.sciencedirect.com/science/article/pii/S2211124715013224 |
| spellingShingle | Ning Li Maryam Yousefi Angela Nakauka-Ddamba Fan Li Lee Vandivier Kimberly Parada Dong-Hun Woo Shan Wang Ammar S. Naqvi Shilpa Rao John Tobias Ryan J. Cedeno Gerard Minuesa Katz Y Trevor S. Barlowe Alexander Valvezan Sheila Shankar Raquel P. Deering Peter S. Klein Shane T. Jensen Michael G. Kharas Brian D. Gregory Zhengquan Yu Christopher J. Lengner The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins Cell Reports |
| title | The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins |
| title_full | The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins |
| title_fullStr | The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins |
| title_full_unstemmed | The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins |
| title_short | The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins |
| title_sort | msi family of rna binding proteins function redundantly as intestinal oncoproteins |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715013224 |
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