ST3GAL4 promotes tumorigenesis in breast cancer by enhancing aerobic glycolysis.

Abstract

Sialyltransferases are enzymes that play a crucial role in regulating cancer progression by modifying glycoproteins through sialylation. In particular, the ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) enzyme is known to be upregulated in breast cancer, but its specific biological functions have not been fully understood. This study aimed to investigate the impact and mechanisms of ST3GAL4 on aerobic glycolysis in breast cancer. We examined ST3GAL4 expression in tumor tissue samples and breast cancer cell lines and also manipulated ST3GAL4 expression in breast cancer cells using lentivirus transduction. The study evaluated cellular processes such as cell viability, cell cycle progression, and aerobic glycolysis by measuring parameters like extracellular acidification rate, glucose uptake, lactate production, and lactate dehydrogenase A (LDHA) expression. We found that ST3GAL4 expression was consistently increased in tumor tissues and breast cancer cell lines. High ST3GAL4 expression was associated with a poor prognosis for patients with breast cancer. Inhibiting ST3GAL4 expression decreased cell viability, disrupted cell cycle progression, and reduced aerobic glycolysis and LDHA expression. Furthermore, suppressing ST3GAL4 expression in animal models reduced tumor growth and cell proliferation. Conversely, overexpressing ST3GAL4 promoted cell viability and cell cycle progression, but these effects were reversed when an inhibitor of aerobic glycolysis was used. The study provided evidence in cells and animal models that ST3GAL4 promotes tumorigenesis in breast cancer by enhancing aerobic glycolysis. These findings suggest that targeting ST3GAL4 may be a potential strategy for the treatment of breast cancer.