NNMT Promotes Epigenetic Remodeling in Cancer by Creating a Metabolic Methylation Sink

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2013 Mar 5

PMID 23455543

Citations 227

Authors

Olesya A Ulanovskaya

Andrea M Zuhl

Benjamin F Cravatt

Affiliations

Soon will be listed here.

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.

Citing Articles

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