Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway
Overexpression of MIST1 reverses the epithelial-mesenchymal transition and reduces the tumorigenicity of pancreatic cancer cells via the Snail/E-cadherin pathway
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MIST1 的过度表达可逆转上皮间质转化，并通过 Snail/E-钙粘蛋白途径降低胰腺癌细胞的致瘤性。
DOI：
10.1016/j.canlet.2018.05.043
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Chunyou
中科院分区：
文献类型：
--
作者：
Li, Xiaogang;Chen, Hengyu;Wang, Chunyou
转录因子在癌症中的作用引起了人们的广泛关注。尽管遗传模型表明MIST1在小鼠中具有肿瘤抑制作用，但其在人类胰腺癌中的作用尚不清楚。我们探讨了MIST1在胰腺癌中的表达和功能。对三个GEO数据集（GSE16515、GSE15471和GSE62165）的分析显示，与正常胰腺组织相比，MIST1 mRNA在人胰腺癌中显著下调。此外，与正常细胞相比，胰腺癌细胞系中MIST1蛋白和mRNA的表达下调。免疫组织化学证实，MIST1在人胰腺癌组织（n = 47）中下调，并与分化有关。在体外，MIST1的过表达减少了胰腺癌细胞的生长、迁移和侵袭。在体内，MIST1的过表达延缓了肿瘤异种移植物的生长，减少了肿瘤细胞向肝脏的播散。此外，MIST1通过下调Snail和上调E-cadherin来逆转上皮-间质转化。E-cadherin的下调促进过表达MIST1的癌细胞的迁移和侵袭。总之，本研究表明，恢复MIST1的表达可以部分通过Snail/E-cadherin途径逆转EMT并降低胰腺癌细胞的致瘤性。
The role of transcription factors in cancer has attracted significant attention. Although genetic models indicate MIST1 functions as a tumor suppressor in mice, its role in human pancreatic cancer is unclear. We explored the expression and function of MIST1 in pancreatic cancer. Analysis of three GEO datasets (GSE16515, GSE15471, and GSE62165) showed MIST1 mRNA was significantly downregulated in human pancreatic cancer compared to normal pancreatic tissues. Moreover, MIST1 protein and mRNA expression were downregulated in pancreatic cancer cell lines compared to normal cells. Immunohistochemistry confirmed MIST1 was downregulated in human pancreatic cancer tissues (n = 47) and associated with differentiation. In vitro, overexpression of MIST1 reduced pancreatic cancer cell growth, migration, and invasion. In vivo, overexpression of MIST1 retarded tumor xenograft growth and decreased tumor cell dissemination to the liver. Furthermore, MIST1 reversed the epithelial-mesenchymal transition by downregulating Snail and upregulating E-cadherin. Knockdown of E-cadherin promoted the migration and invasion of cancer cells overexpressing MIST1. In conclusion, this study indicates restoring the expression of MIST1 reversed the EMT and reduced the tumorigenicity of pancreatic cancer cells partly via the Snail/E-cadherin pathway.