<p>MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial–Mesenchymal Transition In Gastric Cancer</p>

Abstract

BackgroundMetastasis 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.MethodsThe 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.ResultsIt 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.ConclusionOur 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.

RETRACTED ARTICLE: Upregulation of oxidative stress-responsive 1(OXSR1) predicts poor prognosis and promotes hepatocellular carcinoma progression

“…These results implied that OXSR1 is a potential biomarker for HCC. GCKs are related to multiple cellular functions including cell migration, growth and immune regulation, and many members of GCKs family participate in the progression of malignant tumors [25][26][27]. For instance, SPAK, a member of GCK-IV subfamily as well as OXSR1, was found to promote KCC3mediated aggressiveness of cervical cancer through the NF-κB/p38 MAPK/MMP2 axis [27].…”

MST4 inhibits human hepatocellular carcinoma cell proliferation and induces cell cycle arrest via suppression of PI3K/AKT pathway

“…It is known that MST4 promoted the progression of prostate cancer and EMT and tumor metastasis of HCC and gastric cancer by activating p-ERK pathway 13 , 25 . For pancreatic cancer, MST4 interacted with MOB4 to form MST4-MOB4 complex, which antagonized MST1-MOB1 complex to positively regulate YAP activity, thus promoting the cell migration and proliferation 11 .…”

“…For instance, STRIPAK complex was demonstrated to regulate breast cancer cell migration and metastasis by controlling MST4 activity 12 . In gastric cancer, MST4 is reported to facilitate p-ERK pathway thus promoting epithelial-mesenchymal transition (EMT) and metastasis 13 . In glioblastoma, the expression of MST4 is related to the induction of tumor autophagy and can lead to tumorigenesis 14 .…”

Targeting Cytoprotective Autophagy to Enhance Anticancer Therapies

“…The serine/threonine protein kinase MST4, also known as mammalian STE20-like protein kinase 4 (MST4) ( 75 ), was reported to facilitate p-ERK pathway and promote epithelial to mesenchymal transition (EMT) and cancer metastasis in gastric cancer ( 76 ). MST4 is associated with prostate cancer, hepatocellular carcinoma, and breast cancer progression ( 77 , 78 ).…”