Resumen
Peritoneum is the most common metastasis site of gastric cancer, and angiogenesis plays a key role in peritoneal metastasis which the specific mechanism of is unknown. We focused on the peritoneal metastasis-associated secretory protein ESM1 based on the previous RNA-seq. The expression of ESM1 is up-regulated in gastric cancer tissues, and even higher in primary gastric cancer with peritoneal metastasis. Moreover, the high expression of ESM1 is significantly associated with poor prognosis. Through clinicopathological data analysis, it was found that ESM1 was positively correlated with vascular invasion. The conditioned medium of gastric cancer cells overexpressing ESM1 promoted tube formation in vitro and gastric cancer cells overexpressing ESM1 induced angiogenesis in vitro. Mechanically, ESM1 binds to c-Met receptor on the surface of endothelial cells, activates the downstream MAPK/ERK signaling pathway, and promotes the transcription and translation of pro-angiogenic molecules (such as HIF1a, VEGFA and MMP9) in endothelial cell, thereby promoting peritoneal metastasis of gastric cancer. Our study may provide a new direction for the diagnosis and treatment of peritoneal metastasis of gastric cancer.