IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1
- Massachusetts General Hospital, United States
- Broad Institute of Harvard and MIT, United States
- University of Oxford, United Kingdom
Abstract
The gene encoding the Insulin-like Growth Factor 2 mRNA binding protein 2/IMP2 is amplified and overexpressed in many human cancers, accompanied by a poorer prognosis. Mice lacking IMP2 exhibit a longer lifespan and a reduced tumor burden at old age. Herein we show in a diverse array of human cancer cells that IMP2 overexpression stimulates and IMP2 elimination diminishes proliferation by 50-80%. In addition to its known ability to promote the abundance of Insulin-like Growth Factor 2/IGF2, we find that IMP2 strongly promotes IGF action, by binding and stabilizing the mRNA encoding the DNA binding protein HMGA1, a known oncogene. HMGA1 suppresses the abundance of IGF binding protein 2/IGFBP2 and Grb14, inhibitors of IGF action. IMP2 stabilization of HMGA1 mRNA plus IMP2 stimulated IGF2 production synergistically drive cancer cell proliferation and account for IMP2's tumor promoting action. IMP2's ability to promote proliferation and IGF action requires IMP2 phosphorylation by mTOR.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK17776)
- Joseph Avruch
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK057521)
- Joseph Avruch
National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK040561)
- Ruslan I Sadreyev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jeffrey Settleman, Calico Life Sciences, United States
Version history
- Received: March 24, 2017
- Accepted: July 23, 2017
- Accepted Manuscript published: July 28, 2017 (version 1)
- Version of Record published: August 24, 2017 (version 2)
- Version of Record updated: August 29, 2017 (version 3)
Copyright
© 2017, Dai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1
eLife 6:e27155.
https://doi.org/10.7554/eLife.27155
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