The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins
| Autor: | Angela Nakauka-Ddamba, Kimberly Parada, Raquel P. Deering, John W. Tobias, Brian D. Gregory, Shan Wang, Ning Li, Gerard Minuesa, Shilpa Rao, Fan Li, Trevor S. Barlowe, Lee E. Vandivier, Michael G. Kharas, Maryam Yousefi, Ryan J. Cedeno, Yarden Katz, Dong Hun Woo, Shane T. Jensen, Sheila Shankar, Alexander J. Valvezan, Ammar S. Naqvi, Christopher J. Lengner, Peter S. Klein, Zhengquan Yu |
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| Rok vydání: | 2015 |
| Předmět: |
Transplantation
Heterologous Mice Nude RNA-binding protein Mice Transgenic Nerve Tissue Proteins Biology Mechanistic Target of Rapamycin Complex 1 Protein Serine-Threonine Kinases medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article Mice Intestinal mucosa RNA interference Genes Reporter Gene expression medicine Animals Humans Intestinal Mucosa lcsh:QH301-705.5 Loss function beta Catenin Mice Knockout TOR Serine-Threonine Kinases PTEN Phosphohydrolase Pyruvate Dehydrogenase Acetyl-Transferring Kinase RNA-Binding Proteins HCT116 Cells Intestinal epithelium 3. Good health Transplantation Disease Models Animal Cell Transformation Neoplastic lcsh:Biology (General) Multiprotein Complexes Cancer research Female RNA Interference Carcinogenesis Colorectal Neoplasms Proto-Oncogene Proteins c-akt |
| Zdroj: | Cell Reports, Vol 13, Iss 11, Pp 2440-2455 (2015) |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2015.11.022 |
| Popis: | SummaryMembers 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. |
| Databáze: | OpenAIRE |
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