Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer.

ABSTRACT: Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases. Here, we find in colorectal cancer cells that even in the absence of IDH mutation, the levels of D-2HG and its enantiomer L-2HG were elevated through glutamine anaplerosis. D-2HG, but not L-2HG, increased the trimethylation of histone H3 lysine 4 of the promoter region of ZE

SUBMITTER: Colvin H 

PROVIDER: S-EPMC5099755 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature