The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins.

Cell Rep
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell Rep
Volume
13
Issue
11
Pages
2440-55
Date Published
2015 Dec 22
ISSN
2211-1247
URL
DOI
10.1016/j.celrep.2015.11.022
PubMed ID
26673327
PubMed Central ID
PMC4894540
Links
Grant list
P30 DK050306 / DK / NIDDK NIH HHS / United States
R01 CA168654 / CA / NCI NIH HHS / United States
P30-DK050306 / DK / NIDDK NIH HHS / United States