TDO2 knockdown inhibits colorectal cancer progression via TDO2–KYNU–AhR pathway

•The expression of TDO2 in colorectal cancer is higher than that in normal tissues.•Invasion and migration of colorectal cancer cells may be affected by the TDO2.•TDO2 may be an indicator of poor prognosis of colorectal cancer.•The expression of Kyn pathway enzymes may have a potential relationship with increased AhR activity. The aim of this study was to explore the expression levels and biological significance of TDO2 in colorectal cancer (CRC). First, we explored the potential oncogenic roles of TDO2 across 33 tumors based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Second, we evaluated TDO2 protein expression in 55 CRC tissue samples and 30 cDNA samples by immunohistochemistry and qPCR. Third, we investigated the effect of TDO2 on CRC cells by cell proliferation, wound healing, invasion, and colony formation assays. Finally, we determined the protein that is most closely associated with TDO2 via bioinformatics analysis, enriched the key pathways, and verified them. The expression level of TDO2 was found to be associated with the tumor clinical stage in CRC. A high expression of TDO2 was associated with a poor outcome in CRC patients. Inhibition of TDO2 expression by RNAi in LoVo and HCT116 cell lines significantly reduced the proliferation, migration, and invasion abilities as well as colony formation abilities of cells. Further, knockdown of TDO2 expression induced inactivation of the TDO2–KYNU–AhR signaling pathway. The results suggest that TDO2 plays an important role in the progression of CRC. Accordingly, TDO2 is a potential therapeutic target in CRC.