RGD Reference Report - Mutations in isocitrate dehydrogenase 2 accelerate glioma cell migration via matrix metalloproteinase-2 and 9. - Rat Genome Database

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Mutations in isocitrate dehydrogenase 2 accelerate glioma cell migration via matrix metalloproteinase-2 and 9.

Authors: Fu, Y  Zheng, Y  Li, K  Huang, R  Zheng, S  An, N  Liang, A 
Citation: Fu Y, etal., Biotechnol Lett. 2012 Mar;34(3):441-6. doi: 10.1007/s10529-011-0800-8. Epub 2011 Nov 22.
RGD ID: 11522738
Pubmed: (View Article at PubMed) PMID:22105553
DOI: Full-text: DOI:10.1007/s10529-011-0800-8

The gene encoding isocitrate dehydrogenase (IDH) is somatically mutated predominantly in secondary glioblastoma multiforme. Glioma-specific mutations in IDH1 always produced a single amino acid substitution at R132, but mutations in IDH2 were exclusively at R172 which was the analogous site to R132 in IDH1. Mutations of IDH1 and IDH2 led to simultaneous loss and gain of activities in the production of alpha-ketoglutarate and 2-hydroxyglutarate, respectively. Matrix metalloproteinases (MMPs) are zinc-dependent endoproteinases involved in the degradation of the extracellular matrix. The exact role of IDH2 mutant on MMPs activity and cell migration has not been fully studied. Here, we show that in response to IDH2 mutations, low levels of alpha-ketoglutarate increased the stabilization of HIF-1alpha which can contribute to tumor growth. Moreover, mutant IDH2-induced HIF-1alpha improved the secretion levels of pro-MMP-2 and pro-MMP-9 as well as the conversion from pro-MMP-2 to its active form, giving C6 glioma cells a higher migration potential. The HIF-1alpha pathway is probably a critical pathway for release of MMPs in the glioma cancer harboring IDH mutant.



Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Idh2  (isocitrate dehydrogenase (NADP(+)) 2)


Additional Information