IDO1-mediated kynurenine production inhibits IGFBP5 signaling to promote 5-fluorouracil-induced senescence escape and chemoresistance in colorectal cancer.

ABSTRACT: Cellular senescence is an irreversible state of growth arrest, and induction of senescence is considered a potential therapeutic strategy against cancer. Indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme catabolizing L-tryptophan into kynurenine, plays a key role in tumor immune tolerance. However, the roles of IDO1 in cellular senescence and chemoresistance remain elusive. Herein, we observed a significant elevation of IDO1 expression in colorectal cancer (CRC) tissues compared to non-neoplastic controls, based on both the GEPIA database and mouse model. Functionally, ectopic expression of IDO1 blunted 5-fluorouracil (5-FU)-induced cell senescence and rendered CRC cells more refractory towards 5-FU treatment, whereas IDO1 silencing resulted in opposing effects. Further studies demonstrated

SUBMITTER: Li Y 

PROVIDER: S-EPMC11477834 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature