@article{5082b244cb6949789121ca7505d65700,
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.",
author = "Ning Li and Maryam Yousefi and Angela Nakauka-Ddamba and Fan Li and Lee Vandivier and Kimberly Parada and Woo, {Dong Hun} and Shan Wang and Naqvi, {Ammar S.} and Shilpa Rao and John Tobias and Cedeno, {Ryan J.} and Gerard Minuesa and Katz Y and Barlowe, {Trevor S.} and Alexander Valvezan and Sheila Shankar and Deering, {Raquel P.} and Klein, {Peter S.} and Jensen, {Shane T.} and Kharas, {Michael G.} and Gregory, {Brian D.} and Zhengquan Yu and Lengner, {Christopher J.}",
note = "Funding Information: We thank members of the University of Pennsylvania Functional Genomics Core, particularly Dr. Jonathan Schug, for assistance with massively parallel sequencing. We thank Drs. Anil Rustgi, John Lynch, and Kathryn Hamilton in the Division of Gastroenterology as well as members of Dr. Igor Brodsky{\textquoteright}s lab in the Department of Pathobiology for reagents and fruitful discussions. M.Y. is funded by a Howard Hughes international student research fellowship. Z.Y. is funded by National Natural Science Foundation of China (NSFC; 81572614) and the National Basic Research Program of China (973 program-2011CB944103 and 2015SKLAB6-16). C.J.L. is funded by a fellowship from the W.W. Smith Charitable Trust, a pilot award from an American Cancer Society Institutional Research Grant, a grant from the Pennsylvania Department of Health (Health Research Formula Fund no. 4100054874), and R01 CA168654 from the National Cancer Institute. This work was supported in part by the NIH/NIDDK Center for Molecular Studies in Digestive and Liver Diseases (NIH-P30-DK050306) and its core facilities, and C.J.L. was supported by the center{\textquoteright}s pilot and feasibility grant program. Publisher Copyright: {\textcopyright} 2015 The Authors.",
year = "2015",
month = dec,
day = "22",
doi = "10.1016/j.celrep.2015.11.022",
language = "English (US)",
volume = "13",
pages = "2440--2455",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",
}