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

Tünde Kovács, Edit Mikó, András Vida, Éva Sebő, Judit Toth, Tamás Csonka, Anita Boratkó, Gyula Ujlaki, Gréta Lente, Patrik Kovács, Dezső Tóth, Péter Árkosy, Borbála Kiss, G. Méhes, James J. Goedert, P. Bai

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 endothelial-to-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.

Original languageEnglish
Article number1300
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Amino Acid Receptors
Cadaverine
Microbiota
Breast Neoplasms
lysine decarboxylase
Metabolome
Escherichia coli Proteins
Feces
Neoplasms
Carcinogenesis
Reference Values
Stem Cells
Neoplasm Metastasis
Cell Line
Survival
DNA
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. / Kovács, Tünde; Mikó, Edit; Vida, András; Sebő, Éva; Toth, Judit; Csonka, Tamás; Boratkó, Anita; Ujlaki, Gyula; Lente, Gréta; Kovács, Patrik; Tóth, Dezső; Árkosy, Péter; Kiss, Borbála; Méhes, G.; Goedert, James J.; Bai, P.

In: Scientific reports, Vol. 9, No. 1, 1300, 01.12.2019.

Research output: Contribution to journalArticle

Kovács, T, Mikó, E, Vida, A, Sebő, É, Toth, J, Csonka, T, Boratkó, A, Ujlaki, G, Lente, G, Kovács, P, Tóth, D, Árkosy, P, Kiss, B, Méhes, G, Goedert, JJ & Bai, P 2019, 'Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors', Scientific reports, vol. 9, no. 1, 1300. https://doi.org/10.1038/s41598-018-37664-7
Kovács, Tünde ; Mikó, Edit ; Vida, András ; Sebő, Éva ; Toth, Judit ; Csonka, Tamás ; Boratkó, Anita ; Ujlaki, Gyula ; Lente, Gréta ; Kovács, Patrik ; Tóth, Dezső ; Árkosy, Péter ; Kiss, Borbála ; Méhes, G. ; Goedert, James J. ; Bai, P. / Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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