UXT-V1 contributes to the malignant phenotypes of colorectal cancer via GSK3β by activating Wnt/β-catenin pathway

Abstract

Abstract Background: Colorectal cancer (CRC) is one of malignant tumors that seriously threatening human health. β-catenin is a central hub in Wnt pathway, aberrant activation of Wnt/β-catenin signaling pathway promotes the tumorigenesis/progression of CRC. Methods and Results: Here we found a β-catenin interactor, UXT-V1, could modulate Wnt signaling. The expression of UXT-V1 mRNA was increased in CRC tissues. Overexpression of UXT-V1 increased the canonical Wnt signaling, as evidenced by Wnt reporter systems and the up-regulation of marker genes including Axin, CyclinD1 and c-Myc. While, knockdown of UXT-V1 impaired the expression of these genes and attenuated Wnt signaling. Mechanistically, overexpression of UXT-V1 could inhibit GSK3β mediated β-catenin phosphorylation and degradation. Knockout of UXT-V1 increased β-catenin phosphorylation, prevented CRC cell growth, and inhibited tumorigenesis in NOD-SCID mice. Conclusions: Taken together, our findings revealed that UXT-V1 could control Wnt signaling through targeting GSK3β mediated β-catenin phosphorylation and degradation, providing a molecular basis for CRC treatment.