Downregulation of Kynurenine 3-Monooxygenase Inhibits cancer stemness-related genes in both human and canine breast tumor cell lines

Abstract

Canine mammary tumors (CMT) and human breast cancer (HBC) are the most frequent cancers in both female dogs and women worldwide, and they share an urgency for the development of effective markers. Overexpression of kynurenine 3-monooxygenase (KMO), a secondary enzyme of the kynurenine pathway, has been shown to indicate poor prognosis in CMT patients. To further investigate the role of KMO in mammary tumor development, we first analyzed the significant pathways related to KMO from the Database for Annotation, Visualization and Integrated Discovery (DAVID). The results revealed that several Kyoto Encyclopedias of Genes and Genomes (KEGG) pathways might correlate with higher KMO expression, including JAK/STAT and NF-κB, two commonly-referenced cancer stem cell pathways. A canine mammary tumor cell line (CMT-1) and a triple-negative breast cancer (TNBC) cell line, MDA-MB-231, were then used to verify the correlation between KMO expression and cancer stemness. A knockdown of KMO expression using shRNA concomitantly reduced the expression of the cancer stem cell markers POU5F1, SOC2, NANOG and KLF4 in both cell lines. The findings suggest that KMO plays a role in cancer stemness in both canine mammary tumors and human breast cancers and might be a potential target for controlling the development of cancer.