GALNT10 Affects O‐Glycosylation of IGFBP7 to Promote Tumor Vascular Remodeling and Metastasis of Ovarian Cancer
ABSTRACT
Tumor metastasis represents a major determinant of prognosis in ovarian cancer. Accumulating evidence has demonstrated that the glycosylation of secretome proteins regulates cell communication in the tumor microenvironment, thereby affecting tumor metastasis; however, the underlying regulatory mechanisms remain unclear. In this study, we observed markedly elevated glycosylation levels in metastatic ovarian cancer and identified GALNT10 as a key glycosyltransferase that promotes EMT of ovarian cancer cells. Furthermore, GALNT10 enhances the extracellular secretion of IGFBP7 through O‐GalNAc glycosylation modification at the T188 site. IGFBP7 subsequently interacts with the CD93 receptor on endothelial cells, leading to vascular remodeling characterized by abnormal vascular formation and impaired vascular maturity. Moreover, we identified the GALNT10 inhibitor Luteolin, which effectively suppresses ovarian cancer metastasis, modulates the immunosuppressive tumor microenvironment through tumor vascular‐immune crosstalk, and exhibits synergistic effects with anti‐PD1 therapy. Collectively, our findings indicate that GALNT10 facilitates ovarian cancer metastasis through the induction of tumor cell EMT and tumor vascular dysfunction, suggesting that GALNT10 inhibitors represent a promising avenue for the development of novel therapeutic strategies in ovarian cancer.
