In our research, we identified TRPS1 R544Q acts as an activator of EMT signaling via upregulating both mRNA and protein levels of ZEB1 in cells harboring the mutated TRPS1. In contrast, silencing of ZEB1 in CRC cells with TRPS1 mutations diminished the aggressive phenotype, supporting the notion that TRPS1 R544Q mutation promoted colorectal cancer metastasis through transcriptional activation of ZEB1. This evidence concerns the gene ZEB1 and colorectal cancer.