SNX5 facilitates the progression of gastric cancer by increasing the membrane localization of LRP5.

Endocytosis is essential for cancer cell motility, which is predominantly mediated by the sorting nexin (SNX) family. Previous studies have demonstrated that SNX5 is elevated in several tumors, while its clinical significance and underlying mechanism in gastric cancer (GC) remain uninvestigated. In this study, we reported that SNX5 is highly expressed in GC and promotes the malignant biological behavior of GC cells. Its upregulation is closely related to poor prognosis in GC patients. Mechanistically, we observed an interaction between SNX5 and low-density lipoprotein receptor-related protein5 (LRP5) in GC cells. SNX5 inhibits LRP5 internalization and promotes its recycling to the cell membrane, which prevents LRP5 from being degraded in the lysosome. The increased membrane localization of LRP5 facilitates β-catenin stabilization, thus activating the Wnt signaling pathway, leading to tumorigenesis and progression.