Targeting Tryptophan Catabolism: A Novel Method to Block Triple-Negative Breast Cancer Metastasis
Abstract
Triple negative breast cancer (TNBC) cells upregulate the kynurenine pathway (KP) in forced suspension culture. The rate limiting enzyme in this pathway, TDO2 is responsible for tryptophan catabolism and production of the metabolite kynurenine (Kyn). Kyn was recently identified as an endogenous ligand for AhR, a transcription factor that was also upregulated in suspension. Kyn activation of AhR promotes motility of glioma cells. AhR is also in many immune cell types and its activation decreases T-cell activity leading to tumor immune escape. The goal of our proposal is to determine if we can target this pathway that may facilitate TNBC metastasis by enabling tumor cell invasiveness, anchorage independence and immune escape. Our hypothesis is that upregulation of kynerinine by TNBC facilitates survival in transit to metastatic sites and immune suppression and thereby mediates the highly metastatic nature of this subtype.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2018
- Accession Number
- AD1057810
Entities
People
- Jennifer K Richer
Organizations
- University of Colorado Boulder