Nicotinamide N-methyltransferase sustains a core epigenetic program that promotes metastatic colonization in breast cancer

ABSTRACT: Metastatic colonization of distant organs accounts for over 90% of deaths related to solid cancers, yet the molecular determinants of metastasis remain poorly understood. Here, we unveil a mechanism of colonization in the aggressive basal-like subtype of breast cancer that is driven by the NAD+ metabolic enzyme nicotinamide N-methyltransferase (NNMT). We demonstrate that NNMT imprints a basal genetic program into cancer cells enhancing their plasticity. Inline, NNMT expression is associated with poor clinical outcome in breast cancer patients. Accordingly, ablation of NNMT dramatically suppresses metastasis formation in pre-clinical mouse models. Mechanistically, NNMT depletion results in a methyl overflow that increases histone H3K9 trimethylation (H3K9me3) and DNA methylation at the prom

SUBMITTER: Dr. Joana Pinto Couto 

PROVIDER: S-SCDT-10_15252-EMBJ_2022112559 | biostudies-other |

REPOSITORIES: biostudies-other