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Promotion of esophageal adenocarcinoma metastasis via Wnt/ß‐catenin signal pathway by sorting nexins 3
Author(s) -
Pan Biran,
Liu Lei,
Hu Xia,
Sun Xiaobin,
Zhu Yifang,
Zhang Tongtong,
Wei Danfeng,
Guo Yuanbiao,
Shan Jing
Publication year - 2020
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.15039
Subject(s) - wnt signaling pathway , cancer research , metastasis , medicine , adenocarcinoma , catenin , immunohistochemistry , beta catenin , pathology , signal transduction , cancer , biology , microbiology and biotechnology
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.