This study reveals that a novel TOX3-WDR5-H3K4me3/ABCG2 signaling axis is upregulated in colorectal cancer (CRC) stem cells; these proteins show potential as biomarkers for predicting survival of CRC patients, and targeting the pathway may help overcome the challenges of drug tolerance, recurrence and metastasis. This evidence concerns the gene WDR5 and colorectal cancer.