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TSPAN9 和 EMILIN1 通过增加 TSPAN9 的表达协同抑制胃癌细胞的迁移和侵袭。

TSPAN9 and EMILIN1 synergistically inhibit the migration and invasion of gastric cancer cells by increasing TSPAN9 expression.

机构信息

Qingdao University, Qingdao, Shandong, China.

Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

出版信息

BMC Cancer. 2019 Jun 26;19(1):630. doi: 10.1186/s12885-019-5810-2.

DOI:10.1186/s12885-019-5810-2
PMID:31242895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6595627/
Abstract

BACKGROUND

Globally, 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.

METHODS

Human 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 of TSPAN9, 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 following EMILIN1 over-expression.

RESULTS

Inhibiting 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.

CONCLUSIONS

We 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.

摘要

背景

全球范围内，胃癌的发病率和死亡率都很高，其预后不良与肿瘤复发和转移密切相关。因此，与胃癌细胞迁移和侵袭相关的分子机制对于胃癌的治疗至关重要。先前有研究报道 TSPAN9 可抑制胃癌细胞迁移，但其潜在的分子机制尚不清楚。

方法

体外培养人胃腺癌 SGC7901 和 AGS 细胞系。采用 RT-PCR、Western blot 分析和免疫组织化学法检测胃癌及癌旁组织中 TSPAN9 的表达。过表达和敲低 TSPAN9 后，进行划痕愈合和细胞侵袭实验，评估 EMT 相关蛋白表达，分析胃癌细胞的侵袭和迁移能力。通过过表达 EMILIN1 观察 TSPAN9 表达和胃癌细胞的侵袭转移的功能实验。

结果

抑制 TSPAN9 表达可显著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 表达密切相关。并且，EMILIN1 可以协同增强 TSPAN9 的抑瘤作用，这可能是通过促进 TSPAN9 的表达产生的。

结论

我们证实 EMILIN1 通过上调胃癌中 TSPAN9 的表达发挥抗肿瘤作用。因此，膜蛋白 TSPAN9 和 EMILIN1 可能成为治疗胃癌的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/d9a295326c71/12885_2019_5810_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/842fb96eb273/12885_2019_5810_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/be9810f1867b/12885_2019_5810_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/b1340105c59e/12885_2019_5810_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/ec53b0765e04/12885_2019_5810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/d9a295326c71/12885_2019_5810_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/842fb96eb273/12885_2019_5810_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/be9810f1867b/12885_2019_5810_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/b1340105c59e/12885_2019_5810_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/ec53b0765e04/12885_2019_5810_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6994/6595627/d9a295326c71/12885_2019_5810_Fig5_HTML.jpg

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