SDCBP Orchestrated Gastric Cancer Aggression Through Epithelial- Mesenchymal Transition and Macrophages M2 Polarization.

Abstract

Gastric cancer remains a significant global health burden with limited treatment options and high mortality. Syndecan-binding protein (SDCBP), a scaffolding protein involved in tumor differentiation, has attracted attention as a potential therapeutic target in cancers. However, its precise role in gastric cancer progression is not fully understood. In this study, through bioinformatics analysis and gastric cancer samples detection, we discovered that SDCBP was highly expressed in gastric cancer tissues, which was correlated with clinicopathological features such as tumor invasion depth and distant metastasis, and exhibited heterogeneity across histological or molecular subtypes. Elevated SDCBP expression promoted the proliferation, invasion and migration of gastric cancer cells, and modulated epithelial-mesenchymal transition (EMT) via the ERK signaling pathway. Xenograft experiments in mice confirmed that inhibiting SDCBP or ERK signaling could delay cancer progression. We also found that gastric cancer cells with SDCBP knockdown were able to inhibit the M2 polarization of cocultured macrophages, reduce chemotaxis and enhance phagocytosis of macrophages. Therefore, SDCBP plays a crucial role in driving gastric cancer progression. Targeting SDCBP in gastric cancer can partially reverse the malignant phenotype, and SDCBP is expected to be a promising therapeutic target for gastric cancer.