The Msi family of RNA-binding proteins function redundantly as intestinal oncoproteins Journal Article
| Authors: | Li, N.; Yousefi, M.; Nakauka-Ddamba, A.; Li, F.; Vandivier, L.; Parada, K.; Woo, D. H.; Wang, S.; Naqvi, A. S.; Rao, S.; Tobias, J.; Cedeno, R. J.; Minuesa, G.; Katz, Y.; Barlowe, T. S.; Valvezan, A.; Shankar, S.; Deering, R. P.; Klein, P. S.; Jensen, S. T.; Kharas, M. G.; Gregory, B. D.; Yu, Z.; Lengner, C. J. |
| Article Title: | The Msi family of RNA-binding proteins function redundantly as intestinal oncoproteins |
| Abstract: | 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. © 2015 The Authors. |
| Keywords: | protein kinase b; controlled study; protein expression; unclassified drug; oncoprotein; gene deletion; cancer growth; nonhuman; protein function; colorectal cancer; animal cell; mouse; allele; animal tissue; reverse transcription polymerase chain reaction; gene expression; animal experiment; animal model; carcinogenesis; rna binding protein; cancer cell; mammalian target of rapamycin complex 1; intestine epithelium; priority journal; article; protein msi1; protein msi2; protein pdk |
| Journal Title: | Cell Reports |
| Volume: | 13 |
| Issue: | 11 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2015-12-22 |
| Start Page: | 2440 |
| End Page: | 2455 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2015.11.022 |
| PROVIDER: | scopus |
| PUBMED: | 26673327 |
| PMCID: | PMC4894540 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 February 2016 -- Source: Scopus |
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