Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors

Kovács, Tünde and Mikó, Edit and Vida, András and Sebő, Éva and Toth, Judit and Csonka, Tamás and Boratkó, Anita and Ujlaki, Gyula and Lente, Gréta and Kovács, Patrik and Tóth, Dezső and Árkosy, Péter and Kiss, Borbála and Méhes, Gábor and Goedert, James and Bai, Peter (2019) Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. SCIENTIFIC REPORTS, 9. No.-1300. ISSN 2045-2322

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Abstract

Recent studies showed that changes to the gut microbiome alters the microbiome-derived metabolome, potentially promoting carcinogenesis in organs that are distal to the gut. In this study, we assessed the relationship between breast cancer and cadaverine biosynthesis. Cadaverine treatment of Balb/c female mice (500 nmol/kg p.o. q.d.) grafted with 4T1 breast cancer cells ameliorated the disease (lower mass and infiltration of the primary tumor, fewer metastases, and lower grade tumors). Cadaverine treatment of breast cancer cell lines corresponding to its serum reference range (100–800 nM) reverted endothelialto- mesenchymal transition, inhibited cellular movement and invasion, moreover, rendered cells less stem cell-like through reducing mitochondrial oxidation. Trace amino acid receptors (TAARs), namely, TAAR1, TAAR8 and TAAR9 were instrumental in provoking the cadaverine-evoked effects. Early stage breast cancer patients, versus control women, had reduced abundance of the CadA and LdcC genes in fecal DNA, both responsible for bacterial cadaverine production. Moreover, we found low protein expression of E. coli LdcC in the feces of stage 1 breast cancer patients. In addition, higher expression of lysine decarboxylase resulted in a prolonged survival among early-stage breast cancer patients. Taken together, cadaverine production seems to be a regulator of early breast cancer.

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