J Cancer 2021; 12(15):4574-4584. doi:10.7150/jca.59138

Research Paper

Mist1 Inhibits Epithelial-Mesenchymal Transition in Gastric Adenocarcinoma via Downregulating the Wnt/β-catenin Pathway

Xin Xie1, Zhangjian Zhou2, Yongchun Song1, Xin Zhang1, Chengxue Dang1✉, Hao Zhang1✉

1. Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
2. Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.

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Citation:
Xie X, Zhou Z, Song Y, Zhang X, Dang C, Zhang H. Mist1 Inhibits Epithelial-Mesenchymal Transition in Gastric Adenocarcinoma via Downregulating the Wnt/β-catenin Pathway. J Cancer 2021; 12(15):4574-4584. doi:10.7150/jca.59138. Available from https://www.jcancer.org/v12p4574.htm

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Abstract

As a secretory cell transcription factor, muscle intestine stomach expression 1 (Mist1) is associated with serous secretory cell development and gastric chief cell maturation. Here, we focus on the function of Mist1 in gastric adenocarcinoma carcinogenesis. Based on clinical data and a mouse model of gastric cancer, we found that Mist1 expression was reduced in gastric cancer. Then, we overexpressed Mist1 using a lentivirus system and found that overexpression of Mist1 could inhibit gastric cancer cell proliferation, migration and invasion in vitro. Additionally, in vivo, we assessed the function of Mist1 in a gastric cancer xenograft model and distant pulmonary metastasis model. Overexpression of Mist1 decreased tumour growth and distant metastasis in vivo, suggesting that Mist1 acts as a tumour suppressor in gastric carcinogenesis. Furthermore, Mist1 overexpression inhibited epithelial-mesenchymal transition (EMT) in gastric cancer by suppressing β-catenin transcription activity and then the Wingless and INT-1 (Wnt)/β-catenin signalling pathway, which could be reversed by a Wnt/β-catenin-specific agonist. In conclusion, this study indicated that overexpression of Mist1 could reverse EMT in gastric carcinogenesis by inhibiting the Wnt/β-catenin signalling pathway and that Mist1 might be a novel marker for early gastric cancer screening.

Keywords: Mist1, gastric cancer, EMT, Wnt/β-catenin signalling pathway