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

Congratulations to Joana, Milica, Charly and the co-authors of our latest publication in EMBO Journal!!!

In this study, we unveil a mechanism of colonization in the aggressive basal-like subtype of breast cancer that is driven by the metabolic enzyme nicotinamide N-methyltransferase (NNMT). NNMT expression is associated with poor clinical outcome in breast cancer patients and accordingly, its genetic ablation 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 promoters of PR/SET Domain-5 (PRDM5) and extracellular matrix related genes, whose expression is key for establishing the foreign metastatic niche. These findings reveal a critical activity of the NNMT-PRDM5-COL1A1 axis for cancer cell plasticity and metastasis in basal-like breast cancer.

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