Medical Research Center, The Third People's Hospital of Chengdu, The Second Chengdu Hospital Affiliated to Chongqing Medical University, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China.
Assisted Reproductive Center, The Maternal and Child Health Hospital of Qinzhou, Qinzhou, China.
J Gastroenterol Hepatol. 2020 Dec;35(12):2131-2139. doi: 10.1111/jgh.15039. Epub 2020 May 4.
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.
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.
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.
Our data provided strong evidence that sorting nexins 3 played a critical role in esophageal adenocarcinoma metastasis through Wnt/β-catenin signal pathway.
食管腺癌常导致诊断延迟、预后不良、严重的发病率和高死亡率。Wnt/β-连环蛋白信号通路的异常表达与食管腺癌的发生和转移有关。分选连接蛋白 3 已被证明参与 Wnt 蛋白的分拣，并调节 Wnt/β-连环蛋白信号转导。因此，我们研究了分选连接蛋白 3 在食管腺癌中的作用和分子机制。
组织微阵列分析用于分析食管腺癌组织中分选连接蛋白 3 的表达及其与生存率的关系。通过体内和体外模型，我们进一步研究了分选连接蛋白 3 对肿瘤生长和转移的影响及其潜在机制。
免疫组织化学染色的人食管腺癌组织微阵列显示食管腺癌组织中分选连接蛋白 3 水平升高，分选连接蛋白 3 的高表达与预后不良相关。体外研究表明，分选连接蛋白 3 敲低抑制了食管腺癌细胞的侵袭、转移和上皮-间充质转化（EMT）过程，体内肿瘤转移实验也证实了这一结果。此外，我们进一步证明，分选连接蛋白 3 通过 Wnt/β-连环蛋白信号通路影响细胞侵袭和 EMT。
我们的数据提供了强有力的证据表明，分选连接蛋白 3 通过 Wnt/β-连环蛋白信号通路在食管腺癌转移中发挥关键作用。
