Abstract
Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, with peritoneal metastasis commonly seen in advanced cases. Based on RNA-sequencing data from GEO dataset, we focused on the role of SMOC2, SPARC-related modular calcium-binding protein 2, in regulating GC progression and peritoneal metastasis. Our analysis revealed that high SMOC2 expression was associated with poor survival in the population with peritoneal metastases. Functional assays demonstrated that SMOC2 promotes the migration and invasion of GC cells in vitro. In vivo experiments using a mouse peritoneal metastasis model showed that SMOC2 promoted the peritoneal metastasis of GC cells. Additionally, in a co-culture system of GC cells and endothelial cells, SMOC2 overexpression in GC cells promoted the proliferation, migration, and tube formation capability of endothelial cells. Mechanistically, SMOC2 knockdown reduced GSK-3β phosphorylation and nuclear β-catenin levels, accompanied by decreased expression of downstream target genes. These results indicate that SMOC2 promotes GC peritoneal metastasis involving Wnt/β-catenin pathway modulation. In conclusion, our findings highlight SMOC2's significant role in GC progression, potentially involving Wnt/β-catenin pathway modulation and angiogenesis. These results position SMOC2 as a potential prognostic biomarker and therapeutic target for GC peritoneal metastasis.