IGF2 mRNA binding protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1
Open accessAbstract
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.
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Across many cancer subtypes, IMP2 promotes cell growth and proliferation by binding and stabilizing the mRNA of HMGA1.
“across many cancer subtypes, IMP2 promotes cell growth and proliferation by binding and stabilizing the mRNA of HMGA1, a chromatin remodeling protein and established oncogene.”
From IMPlications of IMP2 in RNA Biology and Disease (2025) · cites this paper as [84]
HMGA1 suppresses IGFBP2, which normally binds and sequesters IGF2, allowing more IGF2 to reach and bind to its respective receptors, InsulinR-A and IGF1R.
“HMGA1 suppresses IGFBP2, which normally binds and sequesters IGF2, allowing more IGF2 to reach and bind to its respective receptors, InsulinR-A and IGF1R [84].”
From IMPlications of IMP2 in RNA Biology and Disease (2025) · cites this paper as [84]
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“Funder Grant reference number Author 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 Sadreyev The f…”
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mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry
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- Authors
- Dai, N., Ji, F., Wright, J., Minichiello, L., Sadreyev, R., & Avruch, J.
- Affiliations
- Harvard University (US)
- Broad Institute (US)
- University of Oxford (GB)
- Corresponding author
- Avruch, Joseph
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-07-28
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5576481
- OpenAlex
- W2740881335
- Cited by
- 103
- References
- 5
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 12 · 2022: 16 · 2021: 15 · 2020: 9 · 2019: 13 · 2018: 13 · 2017: 1
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R37 DK17776, P30 DK057521, P30 DK040561)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- IGF2BP2, insulin-like growth factor II, HMGA1, mRNA stabilization, tumor cell proliferation, tumor promotion, IGF signaling, IGF binding protein-2, Grb14, mTOR phosphorylation, oncogenes, mRNA-binding proteins
- MeSH terms
- Animals, Binding Sites, Embryo, Mammalian, Fibroblasts, HeLa Cells, Humans, Insulin-Like Growth Factor II, Phosphorylation, Protein Binding, RNA, Messenger, Signal Transduction, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, HMGA1a Protein, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice, TOR Serine-Threonine Kinases, Primary Cell Culture
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