PRSS2 regulates EMT and metastasis via MMP-9 in gastric cancer.

Serine protease 2 (PRSS2) is upregulated in gastric cancer tissues, correlates with poor prognosis and promotes migration and invasion of gastric cancer cells. However, the exact mechanism by which PRSS2 promotes metastasis in gastric cancer is unclear. We examined serum PRSS2 levels in healthy controls and gastric cancer patients by enzyme linked immunosorbent assay (ELISA) and analyzed the correlation between PRSS2 serum level with the clinicopathological characteristics of gastric cancer patients and matrix metalloproteinase-9 (MMP-9) expression. A lentiviral MMP-9 overexpression vector was constructed and used to transfect gastric cancer cells with stable silencing of PRSS2, and migration, invasion and epithelial-mesenchymal transition (EMT) of gastric cancer cells were examined. High serum PRSS2 levels were detected in gastric cancer patients and associated with lymphatic metastasis and TNM stage. Serum PRSS2 was positively correlated with serum MMP-9 level. PRSS2 silencing inhibited EMT, and knock-down of PRSS2 partially abrogated cell metastasis and EMT caused by overexpression of MMP-9. These results suggest that PRSS2 promotes the migration and invasion of gastric cancer cells through EMT induction by MMP-9. Our findings suggest that PRSS2 may be a potential early diagnostic marker and therapeutic target of gastric cancer.