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

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

doi:10.1016/j.celrep.2015.11.022

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

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. JensenMichael G. Kharas, Brian D. Gregory, Zhengquan Yu, Christopher J. Lengner

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2440-2455
Number of pages	16
Journal	Cell Reports
Volume	13
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2015.11.022
State	Published - Dec 22 2015
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2015.11.022

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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., Y, K., Barlowe, T. S., Valvezan, A., Shankar, S., Deering, R. P., Klein, P. S., ... Lengner, C. J. (2015). The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins. Cell Reports, 13(11), 2440-2455. https://doi.org/10.1016/j.celrep.2015.11.022

@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 = "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",

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Li, N, Yousefi, M, Nakauka-Ddamba, A, Li, F, Vandivier, L, Parada, K, Woo, DH, Wang, S, Naqvi, AS, Rao, S, Tobias, J, Cedeno, RJ, Minuesa, G, Y, K, Barlowe, TS, Valvezan, A, Shankar, S, Deering, RP, Klein, PS, Jensen, ST, Kharas, MG, Gregory, BD, Yu, Z & Lengner, CJ 2015, 'The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins', Cell Reports, vol. 13, no. 11, pp. 2440-2455. https://doi.org/10.1016/j.celrep.2015.11.022

TY - JOUR

T1 - The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins

AU - Li, Ning

AU - Yousefi, Maryam

AU - Nakauka-Ddamba, Angela

AU - Li, Fan

AU - Vandivier, Lee

AU - Parada, Kimberly

AU - Woo, Dong Hun

AU - Wang, Shan

AU - Naqvi, Ammar S.

AU - Rao, Shilpa

AU - Tobias, John

AU - Cedeno, Ryan J.

AU - Minuesa, Gerard

AU - Y, Katz

AU - Barlowe, Trevor S.

AU - Valvezan, Alexander

AU - Shankar, Sheila

AU - Deering, Raquel P.

AU - Klein, Peter S.

AU - Jensen, Shane T.

AU - Kharas, Michael G.

AU - Gregory, Brian D.

AU - Yu, Zhengquan

AU - Lengner, Christopher J.

PY - 2015/12/22

Y1 - 2015/12/22

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84952874847&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.11.022

DO - 10.1016/j.celrep.2015.11.022

M3 - Article

C2 - 26673327

AN - SCOPUS:84952874847

SN - 2211-1247

VL - 13

SP - 2440

EP - 2455

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

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

Abstract

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