Overexpression of CST4 promotes gastric cancer aggressiveness by activating the ELFN2 signaling pathway.

Gastric cancer is one of the most lethal malignancies of gastrointestinal cancer and its prognosis remains dismal because of the paucity of effective therapeutic targets. Here, we show that cystatin 4 (CST4) is markedly upregulated in gastric cancer cell lines and clinical tissues. Ectopic expression of CST4 in gastric cancer cells promoted proliferation, migration, and invasion of gastric cancer cells in vitro. Furthermore, CST4 overexpression significantly promoted the tumorigenicity of gastric cancer cells in vivo, whereas silencing endogenous CST4 caused an opposite outcome. In addition, extracellular leucine rich repeat and fibronectin type III domain containing 2 (ELFN2) was identified as a downstream target of CST4 in gastric cancer cells and was positively correlated with ELFN2 expression in gastric cancer tissues. Finally, we demonstrated that CST4 enhanced gastric cancer aggressiveness by regulating ELFN2 signaling. Together, our results provide new evidence that CST4 overexpression promotes the progression of gastric cancer and might represent a novel therapeutic target for its treatment.