Abstract
The Wnt/β-catenin signaling pathway is a well-studied pathway that drives the carcinogenesis and metastasis of colorectal cancer (CRC). The secretion of Wnt proteins is essential for the continuous activation of Wnt/β-catenin signaling in CRC. The secretion of Drosophila wingless, which is homologous to the human Wnt protein, is mediated by sorting nexin 3 (SNX3) in Drosophila; however, the role of SNX3 in CRC remains unknown. In the present study it was demonstrated that SNX3 reduced the migratory and invasive ability of HCT116 human CRC cells, and reversed epithelial-mesenchymal transition (EMT). Conversely, in the HT29 CRC cell line, which endogenously expresses high levels of SNX3, short hairpin RNA or siRNA-mediated knockdown of SNX3 induced EMT, and enhanced cell migration and invasion. In addition, upregulation of SNX3 significantly inhibited metastasis of HCT116 cells to the lungs of mice. These SNX3-mediated effects were associated with downregulation of β-catenin. Taken together, by downregulating β-catenin, SNX3 may mediate EMT and reverse CRC metastasis.