9P - Kynurenine-3-monooxygenase (KMO) protein promotes triple negative breast cancer progression

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer biology
Breast Cancer
Basic Scientific Principles
Presenter Chun-Yu Liu
Citation Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361
Authors C. Liu1, T. Huang1, C. Lee1, W. Wang1, H. Lee2, L. Tseng3
  • 1Oncology, Taipei Veterans General Hospital, 11217 - Taipei/TW
  • 2Department And Institute Of Pharmacology, National Yang-Ming University, 11217 - Taipei/TW
  • 3Surgery, Taipei Veterans General Hospital, 112 - Taipei/TW



Triple-negative breast cancer (TNBC) remains a difficult-to-treat cancer and the biology beneath TNBC is a research interest. Tryptophan-kynurenine metabolism plays an important role in epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and immune escape. Previous studies have focused on the expression and function of the first step and the rate-limiting enzyme in tumor cells, whereas the second step catabolic enzyme kynurenine 3-monooxygenase (KMO) was rarely addressed in tumorigenesis. Hence, we sought to investigate of the mechanism and functions of KMO in TNBC carcinogenesis.


KMO gene alteration and mRNA transcripts were analyzed from the The Cancer Genome Atlas (TCGA) database. MDA-MB-231 and MDA-MB-468 TNBC cell lines were used for in vitro studies. Cell proliferation, colony formation, transwell migration/invasion assays and tumorsphere forming ability were used for functional study. Signal transduction pathways were assessed by Western blot, quantitative real-time PCR and reporter assays. The effect of KMO on tumor growth was tested in nude mice with breast cancer xenografts.


TCGA analysis showed high-frequency of KMO amplification alterations, which was related to poor overall survival in breast cancers. KMO transcripts were up-regulated in the tumor tissues of breast cancers, especially in TNBC. The functional assays showed that ectopic KMO expression promoted tumorigenesis, including cell growth and abilities of colony formation, migration, invasion, and tumorsphere formation. Moreover, western blot analysis revealed expressions of epithelial marker E-cadherin were decreased and mesenchymal markers N-cadherin, and Twist were increased by KMO overexpression in MDA-MB-468 cells. Interestingly, the mRNA and protein levels of pluripotency genes including CD44, Nanog, Oct4, and SOX-2 were also suppressed by KMO knockdown. Data of reporter gene assay showed that the activities of Nanog, Oct4, and SOX-2 promoters were enhanced by KMO overexpression. Furthermore, knockdown KMO decreased the xenografted tumor growth of MDA-MB-468 cells, suggesting its oncogenic role in TNBC.


Our data highlight the novel and critical roles of KMO in TNBC progression and metastasis.

Clinical trial identification

Not applicable

Legal entity responsible for the study

Taipei Veterans General Hospital


Taipei Veterans General Hospital


All authors have declared no conflicts of interest.