Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
Level 5 - mechanism / opinion, no new human data
Preclinical bench, microproteomic, and animal research with no clinical trial data.
PubMed 31043742 · doi:10.1038/s41586-019-1173-8
What was done
Researchers developed a label-free proteomic workflow to analyze approximately 5,000 microdissected formalin-fixed, paraffin-embedded (FFPE) cells from tumor and stromal compartments of high-grade serous carcinoma across progression stages (in situ to metastatic). They conducted functional in vitro assays, epigenetic evaluations, and in vivo metastasis models to characterize the role of stromal nicotinamide N-methyltransferase (NNMT).
What was found
The abstract reports no numeric values, effect sizes, or confidence intervals. Qualitatively, while the tumor epithelial proteome remained stable during progression, metastasis-associated stroma exhibited a conserved signature marked by NNMT upregulation. Stromal NNMT was necessary and sufficient to drive cancer-associated fibroblast (CAF) marker expression, cytokine secretion, and oncogenic extracellular matrix production. In CAFs, NNMT depleted S-adenosylmethionine (SAM) and reduced histone methylation, altering gene expression and promoting ovarian cancer cell migration, proliferation, and in vivo metastatic growth.
Why it matters
It identifies NNMT as a metabolic and epigenetic driver of the CAF phenotype, establishing a mechanistic link between stromal metabolism and ovarian cancer progression that could serve as a target for anti-metastatic therapies.
Limits
The abstract provides no patient sample sizes, clinical demographics, or quantitative outcome metrics. The findings rely on preclinical in vitro and animal models, and therapeutic efficacy or safety of targeting NNMT in human patients remains unproven.
Cited by
- supports High levels of NAD clearance through NNMT consume methyl groups and reduce SAMe.