OBJECTIVE: To investigate the role of ST3 β-galactoside α-2,3-sialyltransferase 1 (ST3Gal1) and vascular endothelial growth factor receptor 2 (VEGF-R2) in endometrioid-type epithelial ovarian cancer (E-OC) because aberrant α2,3-sialylation mediated by ST3Gal1 and VEGF-R2-related angiogenesis is linked with tumor progression. METHODS: ST3Gal1 and VEGF-R2 expression levels were analyzed in E-OC tissues and cell lines. ST3Gal1 knockdown and ST3Gal1 inhibitor soyasaponin I (SsaI) treatment were performed to evaluate the effects of altered sialylation on the VEGF-R2 pathway, downstream Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling, and cell migration/invasion. Co-immunoprecipitation experiments were conducted to confirm the interaction between ST3Gal1 and VEGF-R2. The combination of SsaI and VEGF-R2 inhibitors was assessed using in vitro and in vivo studies. RESULTS: High ST3Gal1 expression was associated with advanced E-OC stage and poorer overall survival in a univariable analysis; however, it did not retain independent prognostic significance in a multivariable analysis. ST3Gal1 knockdown reduced VEGF-R2 expression and inhibited downstream JAK2/STAT3 signaling and suppressed tumor cell migration and invasion. SsaI treatment reduced VEGF-R2 signaling and impaired metastatic potential in vitro. The combined inhibition of ST3Gal1 and VEGF-R2 reduced tumor growth in vivo. CONCLUSIONS: Targeting ST3Gal1-mediated α2,3-sialylation disrupts VEGF-R2 signaling and suppresses metastatic behavior in E-OC models. Although clinical associations suggest a potential link with adverse outcomes, larger studies are required to clarify its independent prognostic significance. Combined inhibition of ST3Gal1 and VEGF-R2 reduced tumor growth in vivo; these findings support further investigations of ST3Gal1 as a potential therapeutic target in E-OC.
Chao et al. (Mon,) studied this question.