SNX10 Is Involved in Ovarian Cancer Cell Metastasis by Repolarizing Tumor-Associated Macrophages Through mTOR1/Lysosomes Pathway.

Background

Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood.

Methods

The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed using single-cell datasets (GSE147082, GSE58937). The Kaplan-Meier Plotter and GEPIA2 databases were used to evaluate SNX10's prognostic relevance. Lentivirus-mediated SNX10 overexpression in THP-1 cells was employed in tumor cell-macrophage co-culture experiments. Transwell assays and flow cytometry assessed SNX10's effects on ovarian cancer cell metastasis and cisplatin-induced apoptosis. RNA sequencing, Western blotting, lysosomal pH detection, lipid droplet staining, and RT-qPCR were performed to explore SNX10's molecular mechanisms in TAM polarization and immune modulation.

Results

SNX10 was specifically expressed in TAMs, promoting their polarization into the M2 phenotype. This enhanced the migration and invasion of ovarian cancer cell lines A2780 and A2780/CP70 while reducing cisplatin-induced apoptosis. SNX10 decreased lipid droplet content, downregulated p-mTOR1, and impaired lysosomal function in TAMs. Additionally, SNX10 differentially modulated PD-L1 mRNA expression in platinum-sensitive and platinum-resistant ovarian cancer cells.

Conclusions

SNX10 regulates the mTOR1/lysosome pathway in TAMs, influencing lipid metabolism and indirectly modulating ovarian cancer cell metastasis. It also alters PD-L1 mRNA expression, suggesting a role in shaping the tumor immune microenvironment.