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IGF2 mRNA Binding Protein-2 is a tumor promoter that drives cancer proliferation through its client mRNAs IGF2 and HMGA1


ABSTRACT: The gene encoding the IGF2 mRNA binding protein-2/IMP2 is amplified and overexpressed in many cancers, accompanied by a poorer prognosis. Mice deficient in IMP2 exhibit a longer lifespan and a reduced tumor burden at old age. Herein we show in a diverse array of cancer cells that IMP2 overexpression stimulates and IMP2 elimination diminishes proliferation by 50-80%. In addition to its known ability to promote IGF2 abundance, we find that IMP2 strongly promotes IGF action, by binding and stabilizing HMGA1 mRNA. The HMGA1 DNA binding protein, a known oncogene, suppresses the abundance of 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 mTOR-catalyzed IMP2 phosphorylation.

ORGANISM(S): Mus

PROVIDER: GSE101311 | GEO | 2017/09/14

SECONDARY ACCESSION(S): PRJNA393990

REPOSITORIES: GEO

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