Nicotinamide N-methyltransferase sustains a core epigenetic programthat promotes metastatic colonization in breast cancer.

Couto J.P. et al.

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. In line, NNMT expression is associated with poor clinical outcomes in patients with breast cancer. 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 promoters of PR/SET Domain-5 (PRDM5) and extracellular matrix-related genes. PRDM5 emerged in this study as a pro-metastatic gene acting via induction of cancer-cell intrinsic transcription of collagens. Depletion of PRDM5 in tumor cells decreases COL1A1 deposition and impairs metastatic colonization of the lungs. These findings reveal a critical activity of the NNMT-PRDM5-COL1A1 axis for cancer cell plasticity and metastasis in basal-like breast cancer.


Share this article

June, 2023


Products used in this publication

  • Mouse IgG
    5-methylcytosine (5-mC) Antibody - clone 33D3
  • Bioruptor Pico
    Bioruptor® Pico 非接触式超声波破碎仪


  • APHL 2024
    Milwaukee, Wisconsin, USA
    May 6-May 9, 2024



The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics