Conclusions
Taken together, we identify Gpx3 as a suppressor of GC metastasis. Above results provide the rationale that regulation of Gpx3 serves as a potential therapeutic option for GC.
Methods
Cell migration and invasion was determined with Transwell chamber assay. Western blotting was used to determine protein expression levels of Gpx3, EMT markers and Wnt signaling related molecules. In vivo metastasis was determined with experiment lung metastasis model in tumor xenografts.
Purpose
Metastasis is the hallmark of gastric cancer (GC) and is the most widely recognized reason for GC-related deaths. However, the underlying mechanism of GC metastasis remains unknown. Herein we sought to investigate the biologic function of Gpx3 in gastric tumor metastasis and the underlying mechanism.
Results
Gpx3 expression was lower in GC patients and GC cell lines when compared with normal tissues and cells. Further studies showed that overexpression of Gpx3 was able to inhibit GC cell migration and invasion whereas Gpx3 knockdown promoted cell migration and invasion. Furthermore, AGS cells overexpressing Gpx3 showed lower metastatic potential when compared with the parental cells. Gpx3 was also found to regulate the expression of EMT markers. Mechanistic study showed that Gpx3 selectively inhibited Wnt/JNK signaling pathway over canonical Wnt/β-catenin pathway. The data revealed that blockade of NFкB and JNK signaling pathway abolished siGpx3-induced cell migration and invasion. Conclusions: Taken together, we identify Gpx3 as a suppressor of GC metastasis. Above results provide the rationale that regulation of Gpx3 serves as a potential therapeutic option for GC.