4ArrayExpress Uploader0humanwild-typeparentalwild-typeparentalIDH1 R132H/+2C11IDH1 R132H/+2C11IDH1 R132H/+2H1IDH1 R132H/+2H1IDH1 R132C/+3A4IDH1 R132C/+3A4wild-type16F8wild-type16F8IDH2 R140Q/+8G12IDH2 R140Q/+8G12IDH2 R140Q/+17H5IDH2 R140Q/+17H5IDH2 R172K/+47C2IDH2 R172K/+47C2IDH2 R172K/+45G3IDH2 R172K/+45G34602arrayexpress_sidhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-41802Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of.../profile/8773/arrayexpressuploader218cancercellepithelial cellDec.12, 2014Falseisocitrata-dehydrogenase-idh-mutations-promote-a-rE-GEOD-41802_A-AFFY-44Isocitrata Dehydrogenase (IDH) Mutations Promote a Reversible ZEB1/mir-200-Dependent Epithelial Mesenchymal Transition (EMT)Sep.19, 2014Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH and 2-HG alter signaling pathways to promote cancer, though, remains unclear. Additionally, there exist relatively few cell lines with IDH mutations. To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic epithelial cell lines with either wild-type IDH1/2 or clinically relevant IDH1/2 mutations. Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation. IDH1/2 mutants that produce high levels of 2-HG cause an epithelial-mesenchymal transition (EMT)-like phenotype, characterized by changes in EMT-related gene expression and cellular morphology. 2-HG is sufficient to recapitulate aspects of this phenotype in the absence of an IDH mutation. In the cells types examined, mutant IDH-induced EMT is dependent on upregulation of the transcription factor ZEB1 and downregulation of the mir-200 family of microRNAs. Furthermore, sustained knockdown of IDH1 in IDH1 R132H mutant cells is sufficient to reverse many characteristics of EMT, demonstrating that continued expression of mutant IDH is required to maintain this phenotype. These results suggest mutant IDH proteins can reversibly deregulate discrete signaling pathways that contribute to tumorigenesis 9 HCT116 isogenic clones with wild-type or IDH1/2 mutations. Samples were analyzed in duplicate.E-GEOD-41802http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-41802/samples/