Furthermore, by using gain- and loss- of- function approaches, our results clearly indicate that GEN-27 inhibits cancer cell proliferation and inactivates Wnt pathway through regulating the p65-CDX2-β-catenin axis, and this is the first report that p65 could increase the activity of β-catenin through down-regulating CDX2 expression at the transcriptional level. Here, RELA is linked to cancer.