By comparing the expression profiles of DPEP1 mRNA and protein in cancer and noncancerous tissues, and characterizing the role of this gene in regulating invasion and metastasis both in vitro and in vivo, we found that DPEP1 regulates E-cadherin plasticity during TGF-β-mediated EMT, and promotes malignant progression in colon cancer. This evidence concerns the gene DPEP1 and colonic neoplasm.