Promotion of esophageal adenocarcinoma metastasis via Wnt/ß-catenin signal pathway by sorting nexins 3

Abstract

Background: Esophageal adenocarcinoma is often associated with late diagnoses, poor prognoses, significant morbidities, and high mortality rates. Aberrant expression of Wnt/β-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/β-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 epithelial-mesenchymal translation (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 EMT through Wnt/β-catenin signal pathway.

Conclusion: Our data provided strong evidence that sorting nexins 3 played a critical role in esophageal adenocarcinoma metastasis through Wnt/β-catenin signal pathway.

Keywords: Wnt/β-catenin; esophageal adenocarcinoma; metastasis; proliferation; sorting nexins 3.