MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial-Mesenchymal Transition In Gastric Cancer

Taiyuan Li; Li Deng; Xin He; Gongan Jiang; Fang Hu; Shanping Ye; Yu You; Jinzhong Duanmu; Hua Dai; Guodong Huang; Cheng Tang; Xiong Lei

doi:10.2147/CMAR.S219689

MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial-Mesenchymal Transition In Gastric Cancer

Cancer Manag Res. 2019 Nov 5:11:9353-9369. doi: 10.2147/CMAR.S219689. eCollection 2019.

Authors

Taiyuan Li^#¹, Li Deng^#², Xin He¹, Gongan Jiang¹, Fang Hu¹, Shanping Ye¹, Yu You³, Jinzhong Duanmu¹, Hua Dai⁴, Guodong Huang¹, Cheng Tang¹, Xiong Lei¹

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China.
² Department of Diagnostic Medical Sonography, Jiangxi Pingxiang People's Hospital, Pingxiang 337000, Jiangxi, People's Republic of China.
³ Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China.
⁴ Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China.

^# Contributed equally.

Abstract

Background: Metastasis is the main cause for gastric cancer (GC)-related deaths. Better understanding of GC metastatic mechanism would provide novel diagnostic markers and therapeutic targets. Though it has been reported that mammalian sterile-20-like kinase 4 (MST4) exerts the oncogenic role in other tumors, the prognostic value and biological role of MST4 in GC are still unknown.

Methods: The expression level of MST4 in GC was analyzed by using TCGA database. Then, Western blot and polymerase chain reaction (PCR) were used to determine the MST4 expression in GC tissues and cell lines. Immunohistochemistry was performed to investigate the expression of proteins in human GC tissues, and its correlation with clinicopathologic parameters as well as the prognosis for patients with GC was analyzed. In addition, the biological function and its molecular mechanism of MST4 in GC were investigated by in vitro and in vivo assays.

Results: It demonstrated that MST4 expression was significantly upregulated in GC tissues and cell lines. High expression of MST4 was correlated with aggressive clinicopathological parameters such as lymph node metastasis, lymphovascular invasion (all P < 0.05). GC patients with high MST4 expression had both shorter overall survival (OS) and disease-free survival (DFS) than those with low MST4 expression (all P < 0.05). MST4 expression was an independent and significant risk factor for OS and DFS of GC patients (all P < 0.05). Results of functional experiments showed that MST4 could promote GC cells migration, invasion in vitro and metastasis in vivo. In terms of mechanism, MST4 promoted metastasis by facilitating epithelial-mesenchymal transition (EMT) through activating Ezrin pathway in GC. Further studies indicate that down-regulated miR-124-3p expression contributes to upregulated MST4 expression in GC.

Conclusion: Our data showed that MST4 predicts poor prognosis and promotes metastasis by facilitating epithelial-mesenchymal transition in GC. Therefore, our study suggests that MST4 can be used as a valuable prognostic biomarker and a potential therapeutic target in GC.

Keywords: MST4; epithelial-mesenchymal transition; gastric cancer; metastasis; prognosis.

Grants and funding

This study was supported by the Natural Science Foundation of Jiangxi, China (grant no. 20181BAB215025), National Natural Science Foundation of China (grant no. 81702922), National Health Commission Foundation of Jiang Xi (grant no. 20191016), Natural Science Fund of Education Department of Jiang Xi (grant no. GJJ170007).