Affiliation:
1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Abstract
The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Social Development Project of Jiangsu Province
Gusu Health Talents Cultivation Program, China
Qinglan Project
Postgraduate Research and Practice Innovation Program of Jiangsu Province
Clinical Medicine peak project of Soochow Medical College, Soochow University
333 Talent Project
Six Talent Peaks Project in Jiangsu Province