Blocking Tryptophan Catabolism Reduces Triple-Negative Breast Cancer Invasive Capacity

Cancer Res Commun. 2024 Oct 1;4(10):2699-2713. doi: 10.1158/2767-9764.CRC-24-0272.

Abstract

TDO2 is more highly expressed than the nonhomologous TRP-catabolizing enzyme IDO1 in TNBC. We find that TDO2 knockdown can lead to a compensatory increase in IDO1. Therefore, we tested a newly developed TDO2/IDO1 dual inhibitor and found that it decreases TRP catabolism, anchorage-independent survival, and invasive capacity.

MeSH terms

  • Cell Line, Tumor
  • Female
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase* / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase* / metabolism
  • Neoplasm Invasiveness*
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / metabolism
  • Tryptophan Oxygenase / antagonists & inhibitors
  • Tryptophan Oxygenase / genetics
  • Tryptophan Oxygenase / metabolism
  • Tryptophan* / metabolism

Substances

  • Tryptophan
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • IDO1 protein, human
  • Tryptophan Oxygenase