sorting nexins 3 promotes esophageal adenocarcinoma metastasis via Wnt/β-catenin signal pathway: sorting nexins 3 promotes esophageal adenocarcinoma metastasis via Wnt/β-catenin signal pathway

BACKGROUND: Esophageal adenocarcinoma is often associated with late diagnoses, poor prognoses, significant morbidities and high mortality rates. Aberrant expression of Wnt/beta-catenin signal pathways were observed in the tumorigenesis and metastasis of esophageal adenocarcinoma. Sorting nexins 3 has been shown to participate in Wnt protein sorting and regulate Wnt/beta-catenin signal transduction. Thus we studied the role and molecular mechanism of sorting nexins 3 in esophageal adenocarcinoma. METHODS: Tissue microassay were used to analyze the expression of sorting nexins 3 in esophageal adenocarcinoma tissue, and its relationship with survival rate. Using in vivo and in vitro models, we further investigated the effect of sorting nexins 3 on tumor growth and metastasis, and underling mechanism. RESULTS: Immunohistochemical staining of human esophageal adenocarcinoma tissue microassay revealed an increased sorting nexins 3 level in esophageal adenocarcinoma tissue and high expression of sorting nexins 3 correlated with the poor prognosis. In vitro study showed that sorting nexins 3 knockdown suppressed esophageal adenocarcinoma cell invasion, metastasis and EMT process, and this result was confirmed by in vivo tumor metastasis assays. Moreover, we further proved that sorting nexins 3 affected cell invasion and epithelial-mesenchymal translation through Wnt/beta-catenin signal pathway. CONCLUSION: Our data provided strong evidence that sorting nexins 3 played a critical role in esophageal adenocarcinoma metastasis through Wnt/beta-catenin signal pathway.