Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.7554/eLife.27155

Type

Journal article

Journal

Elife

Publication Date

28/07/2017

Volume

6

Keywords

Grb14, HMGA1, IGF2, IGF2BP2, IGFBP2, cancer biology, human, mTOR, Adaptor Proteins, Signal Transducing, Animals, Binding Sites, Cell Line, Tumor, Cell Proliferation, Embryo, Mammalian, Fibroblasts, Gene Expression Regulation, Neoplastic, HMGA1a Protein, HeLa Cells, Humans, Insulin-Like Growth Factor II, Mice, Phosphorylation, Primary Cell Culture, Protein Binding, RNA, Messenger, RNA-Binding Proteins, Signal Transduction, TOR Serine-Threonine Kinases