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  • NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink.

NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink.

Nature chemical biology (2013-03-05)
Olesya A Ulanovskaya, Andrea M Zuhl, Benjamin F Cravatt
ABSTRACT

Nicotinamide N-methyltransferase (NNMT) is overexpressed in a variety of human cancers, where it contributes to tumorigenesis by a mechanism that is still poorly understood. Here we show using metabolomics that NNMT impairs the methylation potential of cancer cells by consuming methyl units from S-adenosyl methionine to create the stable metabolic product 1-methylnicotinamide. As a result, NNMT-expressing cancer cells have an altered epigenetic state that includes hypomethylated histones and other cancer-related proteins combined with heightened expression of protumorigenic gene products. Our findings thus point to a direct mechanistic link between the deregulation of a metabolic enzyme and widespread changes in the methylation landscape of cancer cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-PP2A Antibody, C subunit, Upstate®, from rabbit
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