TSPAN9 and EMILIN1 synergistically inhibit the migration and invasion of gastric cancer cells by increasing TSPAN9 expression
TSPAN9 and EMILIN1 synergistically inhibit the migration and invasion of gastric cancer cells by increasing TSPAN9 expression
复制标题
TSPAN9和EMILIN1通过增加TSPAN9表达协同抑制胃癌细胞的迁移和侵袭
DOI：
10.1186/s12885-019-5810-2
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发表时间：
2019-06-26
期刊：
影响因子：
3.8
通讯作者：
Qiu, Wensheng
中科院分区：
文献类型：
--
作者：
Qi, Yaoyue;Lv, Jing;Qiu, Wensheng
研究背景在全球范围内，胃癌的发病率和死亡率较高，其预后不良与肿瘤的复发和转移密切相关。因此，胃癌细胞迁移和侵袭的分子机制对于胃癌的治疗具有重要意义。此前已有报道称TSPAN9可抑制胃癌细胞迁移；方法体外培养人胃腺癌细胞系SGC7901和AGS。通过 RT-PCR、蛋白质印迹分析和免疫组织化学测定胃癌和癌旁组织中的 TSPAN9 表达。过表达和敲低TSPAN9后，进行伤口愈合和细胞侵袭实验，并评估EMT相关蛋白表达，以分析胃癌细胞的侵袭和迁移。通过EMILIN1过表达后的功能检测观察TSPAN9的表达及胃癌细胞的侵袭和转移。结果抑制TSPAN9的表达显着促进胃癌细胞的迁移和侵袭。此外，免疫荧光共定位和免疫共沉淀分析显示EMILIN1和TSPAN9的表达密切相关。此外，EMILIN1可以协同增强TSPAN9的抑癌作用，这可能是通过促进TSPAN9表达而产生的。结论我们已经证明EMILIN1通过上调胃癌中TSPAN9的表达来诱导抗肿瘤作用。因此，膜蛋白 TSPAN9 和 EMILIN1 可能代表胃癌治疗的新靶点。
BackgroundGlobally, the incidence and mortality rates of gastric cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasis. Therefore, the molecular mechanisms associated with the migration and invasion of gastric cancer cells are important for gastric cancer treatment. Previously, TSPAN9 has been reported to inhibit gastric cancer cell migration; however, the underlying molecular mechanism remains unclear.MethodsHuman gastric adenocarcinoma cell lines, SGC7901 and AGS, were cultured in vitro. TSPAN9 expression was determined by RT-PCR, western blot analysis, and immunohistochemistry in gastric cancer and tumor-adjacent tissues. Following the over-expression and knockdown ofTSPAN9, wound healing and cell invasion assays were performed and EMT-related protein expression was evaluated to analyze the invasion and migration of gastric cancer cells. TSPAN9 expression and the invasion and metastasis of gastric cancer cells were observed by the functional assays followingEMILIN1over-expression.ResultsInhibiting TSPAN9 expression significantly promoted the migration and invasion of gastric cancer cells. In addition, immunofluorescence co-localization and co-immunoprecipitation analysis revealed closely related expression of EMILIN1 and TSPAN9. Moreover, EMILIN1 can synergistically boost the tumor suppressive effect of TSPAN9, which may be produced by promoting TSPAN9 expression.ConclusionsWe have demonstrated that EMILIN1 induces anti-tumor effects by up-regulating TSPAN9 expression in gastric cancer. Hence, membrane proteins TSPAN9 and EMILIN1 may represent novel therapeutic targets for the treatment of gastric cancer.